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Human periodontal ligament (hPDL) is continuously exposed to mechanical forces that can induce inflammatory responses in resident stem cells (hPDLSCs). Here, we review the impact of mechanical force on hPDLSCs, focusing on the activation of inflammatory cytokines and related signalling pathways, which subsequently influence periodontal tissue remodelling. The effects of various mechanical forces, including compressive, shear, and tensile forces, on hPDLSCs are discussed. The review highlights the role of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in mediating inflammatory responses, as well as the counteracting effects of anti-inflammatory cytokines like IL-4 and IL-10. Additionally, we underscore the involvement of toll-like receptors (TLRs), particularly TLR4, in transducing mechanical stress signals and modulating cytokine production. This review demonstrates that hPDLSCs respond to different mechanical forces with specific gene expression changes that direct inflammatory and bone remodelling signals, leading to increased osteoblast and osteoclast activity. Moreover, hPDLSCs, together with contiguous hPDL cells, respond to various mechanical forces by regulating the immune function of several immune cells. This complex relationship between the mechanical force stress, inflammation, and the cellular response in hPDLSCs warrants further research to develop therapeutic strategies for periodontal and related diseases.

Mesenchymal stem cells (MSCs) are highly plastic, with the capacity to differentiate into a spectrum of tissue-specific stromal cells. In the field of bone regeneration, MSCs have largely been considered for their osteogenic differentiation capacity. MSCs are increasingly being appreciated for their immunomodulatory potential following exposure to pro-inflammatory stimuli (licensing). Pro-inflammatory environments arise following bone injury via activation of resident immune cells like macrophages. We describe the use of a mineralized collagen scaffold as a bone-mimetic in vitro model to study the influence of paracrine versus direct cell-to-cell contact of THP-1 macrophages on MSC osteogenic and immunomodulatory potential. Paracrine stimuli from macrophages enhance MSC osteogenic and immunomodulatory potential via upregulation of key transcriptomic markers as well as via soluble biomolecule production. Direct co-culture of MSCs and macrophages decreased immunomodulatory potential in MSCs, especially for licensed MSCs, but enhanced matrix remodeling and expression of genes related to macrophage chemotaxis. These data demonstrate the significant effect macrophage-derived paracrine factors and direct contact have on MSC activity in a biomaterial model of bone regeneration. This work illuminates a critical need to further understand these processes in more clinically relevant cell models to inform biomaterial design.

Abstract Background Interaction between mesenchymal stem cells (MSCs) and oral squamous cell carcinoma (OSCC) cells plays a major role in OSCC progression. However, little is known about adipogenic differentiation alteration in OSCC-derived MSCs (OSCC-MSCs) and how these alterations affect OSCC growth. Methods MSCs were successfully isolated and cultured from normal gingival tissue, OSCC peritumoral tissue, and OSCC tissue. This included gingiva-derived MSCs (GMSCs), OSCC adjacent noncancerous tissues-derived MSCs (OSCCN-MSCs), and OSCC-MSCs. The adipogenic and osteogenic differentiation capabilities of these cells were evaluated using Oil Red O and Alizarin Red S staining, respectively. OSCC cells were then co-cultured with either OSCC-MSCs or GMSCs to assess the impact on OSCC cell proliferation and migration. Subcutaneous xenograft experiments were conducted in BALB/c-nu mice to further investigate the effects in vivo. Additionally, immunohistochemical staining was performed on clinical samples to determine the expression levels of fatty acid synthase (FASN) and the proliferation marker Ki67. Results OSCC-MSCs exhibited enhanced adipogenic differentiation and reduced osteogenic differentiation compared to GMSCs. OSCC-MSCs significantly increased the proliferation and migration of OSCC cells relative to GMSCs and promoted tumor growth in mouse xenografts. Lipid droplet accumulation in the stroma was significantly more pronounced in OSCC + OSCC-MSCs xenografts compared to OSCC + GMSCs xenografts. Free fatty acids (FFAs) levels were elevated in OSCC tissues compared to normal gingival tissues. Moreover, OSCC-MSCs consistently secreted higher levels of FFAs in condition medium than GMSCs. Knockdown of FASN in OSCC-MSCs reduced their adipogenic potential and inhibited their ability to promote OSCC cell proliferation and migration. Clinical sample analysis confirmed higher FASN expression in OSCC stroma, correlating with larger tumor size and increased Ki67 expression in cancer tissues, and was associated with poorer overall survival. Conclusions OSCC-MSCs promoted OSCC proliferation and migration by upregulating FASN expression and facilitating FFAs secretion. Our results provide new insight into the mechanism of OSCC progression and suggest that the FASN of OSCC-MSCs may be potential targets of OSCC in the future.

Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs’ secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection. Methods We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection. Results The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines. Conclusions Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy.

Abstract Despite significant strides in medical treatments and surgical procedures for cardiovascular diseases, these conditions continue to be a major global health concern. The persistent need for innovative therapeutic approaches to mend damaged heart tissue highlights the complexity and urgency of this medical challenge. In recent years, stem cells have emerged as a promising tool for tissue regeneration, but challenges such as graft rejection and tumor formation have limited their clinical application. Exosomes, extracellular vesicles containing a diverse array of biomolecules, have garnered significant attention for their potential in regenerative medicine. The cardioprotective and reparative properties of mesenchymal stem cell-derived exosomes hold promise for the treatment of heart diseases. These exosomes can modulate various cellular processes, including angiogenesis, apoptosis, and inflammation, thereby enhancing cardiac function. Despite the growing interest, there remains a lack of comprehensive reviews synthesizing the molecular mechanisms, preclinical, and clinical evidence related to the specific role of MSC-derived exosomes in cardiac therapies. This review aims to fill that gap by exploring the potential of MSC-derived exosomes as a therapeutic strategy for cardiac diseases. This review explores the potential of mesenchymal stem cell-derived exosomes as a therapeutic strategy for cardiac diseases. We discuss the molecular mechanisms underlying their cardioprotective effects, summarize preclinical and clinical studies investigating their efficacy, and address the challenges and future perspectives of exosome-based therapies. The collective evidence suggests that MSC-derived exosomes hold promise as a novel and effective therapeutic approach for cardiac diseases. Graphical abstract

Abstract Background Mesenchymal stem cells have great potential for repairing articular cartilage and treating knee osteoarthritis (KOA). Nonetheless, little is known about the efficacy of human adipose-derived mesenchymal stem cells (haMSCs) for KOA in large animal models. Methods This study evaluated the therapeutic efficacy of haMSCs in knee articular cartilage repair in a sheep model of KOA. haMSCs were isolated, cultured, and characterized. KOA was surgically induced by anterior cruciate ligament transection and medial meniscectomy, followed by intra-articular injection of saline (negative control group) or haMSCs (haMSC group) into the right knee joint at 6 and 9 weeks after surgery. Sheep were sacrificed 21 weeks after surgery, and samples (whole knee joints, femoral condyles, and tibias) were collected, processed, and analyzed. Changes in knee articular cartilage were assessed by magnetic resonance imaging, micro-computed tomography, macroscopic analysis, histology, and immunohistochemistry. Results KOA caused the degeneration of the medial femoral condyle in the sheep model of KOA. Conversely, haMSCs repaired chondral defects and increased the thickness of knee articular cartilage. Conclusions These data suggest that the intra-articular injection of haMSCs can effectively repair articular cartilage defects in the knee.

Abstract Background Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are recognized for their therapeutic potential in immune modulation and tissue repair, especially in veterinary medicine. This study introduces an innovative sequential stimulation (IVES) technique, involving low-oxygen gas mixture preconditioning using in vitro fertilization gas (IVFG) and direct current electrical stimulation (ES20), to enhance the anti-inflammatory properties of sEVs from canine adipose-derived MSCs (cAD-MSCs). Initial steps involved isolation and comprehensive characterization of cAD-MSCs, including morphology, gene expression, and differentiation potentials, alongside validation of the electrical stimulation protocol. IVFG, ES20, and IVES were applied simultaneously with a control condition. Stimulated cAD-MSCs were evaluated for morphological changes, cell viability, and gene expressions. Conditioned media were collected and purified for sEV isolation on Day1, Day2, and Day3. To validate the efficacy of IVES for sEV production, various analyses were conducted, including microscopic examination, surface marker assessment, zeta-potential measurement, protein quantification, nanoparticle tracking analysis, and determination of anti-inflammatory activity. Results We found that IVES demonstrated non-cytotoxicity and induced crucial genotypic changes associated with sEV production in cAD-MSCs. Interestingly, IVFG influenced cellular adaptation, while ES20 induced hypoxia activation. By merging these stimulations, IVES enhanced sEV stability and quality profiles. The cAD-MSC-derived sEVs exhibited anti-inflammatory activity in lipopolysaccharide-induced RAW264.7 macrophages, emphasizing their improved effectiveness without cytotoxicity or immunogenicity. These effects were consistent across day 3 collection, indicating the establishment of an effective protocol for sEV production. Conclusions This research established an innovative sequential stimulation method with positive impact on sEV characteristics including stability, quality, and anti-inflammatory activity. This study not only contributes to the enhancement of sEV production but also sheds light on their functional aspects for therapeutic interventions.

Tusipkhan Toktarov,1,2 Yerik Raimagambetov,1 Bagdat Balbossynov,1 Dina Saginova,1 Mukhtar Abilmazhinov,2 Vyacheslav Ogay1,3 1National Scientific Center of Traumatology and Orthopedics Named After Academician Batpenov N.D., Astana, Kazakhstan; 2Astana Medical University, Astana, Kazakhstan; 3Stem Cell Laboratory, National Center for Biotechnology, Astana, KazakhstanCorrespondence: Tusipkhan Toktarov, Astana Medical University, Beybitshilik 49 A, Astana, Z10K8Y7, Kazakhstan, Tel +77052928127, Email toktarov.tusya@gmail.comBackground: Cartilage defects in the knee joint are areas of damage and wear to the cartilage that normally covers and protects the ends of bones. These defects occur due to sudden injuries, such as trauma or sports accidents, or due to chronic conditions, such as osteoarthritis. Cartilage acts as a shock absorber (cushion absorber), reducing the impact of mechanical stress on the joints, which helps prevent bone damage during movement. Cartilage also serves as a gliding surface for the joints, allowing them to move smoothly, which minimizes friction between the bones. Its damage can cause pain, swelling, and decreased joint function. Treatment of localized cartilage defects is important to prevent further damage to the joint and maintain good knee function. Identifying problems early and treating them correctly can help improve outcomes and reduce the likelihood of more serious joint problems.Case Description: We describe the case of a 46-year-old man with a localized cartilage defect in the knee joint who was followed for one year after the application of heparin-conjugated fibrin hydrogel for the treatment. We watched the patient for a year, doing functional tests, checking MRI results after the procedure, and watching for side effects.Results: This case demonstrates that implantation of hydrogel successfully engraft and lead to remodeling of hyaline-like cartilage, thereby improving the condition of damaged knee cartilage. Comparison of MRI images before and 1 year after surgery showed the effectiveness of this technology.Keywords: cartilage defects, knee joint, mesenchymal stem cells, fibrin hydrogel, growth factors

Abstract Parkinson’s disease (PD) is a progressive disorder that affects the nervous system and causes regions of the brain to deteriorate. In this study, we investigated the effects of MR-guided focused ultrasound (MRgFUS) for the delivery of human mesenchymal stem cells (MSCs) on the 6-hydroxydopamine (6-HODA)-induced PD rat model. MRgFUS-induced blood-brain barrier (BBB) permeability modulation was conducted using an acoustic controller with the targets at the striatum (ST) and SN. Human MSCs were injected immediately before sonication. Here, we show that we can deliver human MSCs into Parkinsonian rats through MRgFUS-induced BBB modulation using an acoustic controller. Stem cells were identified in the sonicated brain regions using surface markers, indicating the feasibility of MSC delivery via MRgFUS. MSCs + FUS treatment significantly improved the behavioural outcomes compared with control, FUS alone, and MSCs alone groups (p

Abstract Objective The direction of this study was to detect and analyze the specific mechanism of anti-apoptosis in mesenchymal stem cells (MSCs) cells caused by high expression of BCL2. Methods Bioinformatics was completed in Link omics. GO analysis and KEGG analysis were carried out, and the grope tool of Link omics database was used to evaluate PPI information and other core path analysis information. The cultured cells were divided into MSC + normoxic group (MSCs were cultured in conventional medium, including 10% depleted serum of fetal bovine exosomes, 37 °C, 5% CO2 and 95% air) and Exo-BCL-2 + MSC + normoxic group (a certain concentration of purified BCL-2 exosomes was co-cultured with MSC in conventional medium, 37 °C, 5% CO2 and 95% air), Exo-BCL-2 + MSC + hypoxia group (a certain concentration of purified BCL-2 exosomes and MSC were co-cultured in hypoxia medium at 37 °C, 80% CO2 and 20% air), MSC + hypoxia group (MSCs were cultured in hypoxia medium with 10% depleted serum of fetal bovine exosomes, 37 °C, 80% CO2 and 20% air), exo WT + MSC + normoxic group (co-cultured with MSC in conventional medium at 37 °C, 5% CO2 and 95% air) and exoWT + MSC + hypoxic group (co-cultured with MSC in hypoxic medium at 37 °C, 80% CO2 and 20%). Cell proliferation ability was monitored by cell proliferation test. Cell migration test was used to check the migration capacity of MSCs. The expressions of apoptosis-related proteins BCL-2, caspase3 and caspase9, Runx2, ALP and PPAR‐γ were analyzed by western blot. Tissue damage was scored by H&E and Ma Song trichrome staining. Masson staining was used to evaluate the collagen volume fraction of the wound. The expressions of KRT14, α‐SMA, CD31 and PCNA in rat trauma tissues were analyzed by immunofluorescence staining. The horizontal of apoptosis-related proteins in skin lesions was checked by Western blot. The horizontal of inflammatory factors TNF-α and IL-6 in traumatic tissue of rats were detected by ELISA. Results From KEGG's results, we can see that BCL2-2 was closely related to base excision and repair, cell cycle, steroid biosynthesis and other pathways. When cultured for 48h and 72h, the proliferation ability and migration number of MSCs in MSC + hypoxia group were lower than MSC + normoxic group, but the expressions of caspase3 and caspase9 were higher. The proliferation ability and migration number of MSCs in Exo-BCL-2 + MSC + hypoxia group and MSC + hypoxia group were lower than those in Exo-BCL-2 + MSC + normoxic group and MSC + normoxic group, and the horizontal of caspase3 and caspase9 were lower. Exo-BCL-2 + MSC + normoxic group increased the proliferation capacity and migration number of MSCs, but decreased the expression of caspase3 and caspase9. Compared with Exo-BCL-2 + MSC + normoxia and Exo-BCL-2 + MSC + normoxia, the proliferation ability and migration quantity of MSCs in exo WT + MSC + normoxia and exo WT + MSC + hypoxia groups were lower, and the horizontal of caspase3 and caspase9 proteins was higher. Conclusion Bioinformatics analysis shows that BCL2-2 plays a worthwhile role in the process of cell apoptosis and proliferation. Exosomes with high expression of BCL-2 can encourage the proliferation of MSC in hypoxic environment. The wound treated with MSCs‐BCL-2 promotes the compose of new blood vessels and granulation tissue in the wound, the redifferentiation of epithelial cells and the remodeling of collagen, which has a high therapeutic prospect for chronic wounds and skin regeneration.

Abstract This study evaluated the efficacy of tubular constructs containing stem cells and Type I collagen, both independently and in conjunction with low-level laser therapy (LLLT), in repairing the sciatic nerve in a rat model. In this animal study, the right sciatic nerve of 30 male Wistar rats, each weighing 250–300 g, was surgically excised to a length of 8 mm. The rats were then randomly allocated to three groups (n = 10 per group). In Group 1, the excised nerve segment was utilized as an autograft and sutured at the defect site. In Group 2, a tubular construct containing stem cells and Type I collagen was used to bridge the proximal and distal ends of the nerve. Group 3 received the same intervention as group 2, supplemented with 5 weeks of LLLT. After 5 and 12 weeks, rats underwent histological, behavioral, and electrophysiological assessments. Data were statistically analyzed using analysis of variance (ANOVA), Bonferroni post-hoc test, and Kruskal–Wallis test. At both 5 and 12 weeks, axonal count and nerve repair scores showed no significant differences among the three groups (P > 0.05). Notably, the Sciatic Functional Index (SFI) was the most favorable (lowest) in the autograft group, whereas the stem cell-only group exhibited the least favorable (highest) SFI at 5 weeks (P

Ting Li,1,2,* Yuechu Zhao,3,* Zhi Cao,2,* Ying Shen,2 Jiaqi Chen,2 Xinran Huang,2 Zhuang Shao,2 Yi Zeng,2 Qi Chen,2 Xiaofei Yan,3 Xin Li,1,2 Yuelin Zhang,1,2 Bei Hu1,2 1School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuelin Zhang; Bei Hu, Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-83827812-20974, Email zhangyuelin1999@163.com; qhubei@hotmail.comBackground: Exosomes sourced from mesenchymal stem cells (MSC-EXOs) have become a promising therapeutic tool for sepsis-induced myocardial dysfunction (SMD). Our previous study demonstrated that Apelin pretreatment enhanced the therapeutic benefit of MSCs in myocardial infarction by improving their paracrine effects. This study aimed to determine whether EXOs sourced from Apelin-pretreated MSCs (Apelin-MSC-EXOs) would have potent cardioprotective effects against SMD and elucidate the underlying mechanisms.Methods: MSC-EXOs and Apelin-MSC-EXOs were isolated and identified. Mice neonatal cardiomyocytes (NCMs) were treated with MSC-EXOs or Apelin-MSC-EXOs under lipopolysaccharide (LPS) condition in vitro. Cardiomyocyte pyroptosis was determined by TUNEL staining. RNA sequencing was used to identify differentially expressed functional miRNAs between MSC-EXOs and Apelin-MSC-EXOs. MSC-EXOs and Apelin-MSC-EXOs were transplanted into a mouse model of SMD induced by cecal ligation puncture (CLP) via the tail vein. Heart function was evaluated by echocardiography.Results: Compared with MSC-EXOs, Apelin-MSC-EXO transplantation greatly enhanced cardiac function in SMD mice. Both MSC-EXOs and Apelin-MSC-EXOs suppressed cardiomyocyte pyroptosis in vivo and in vitro, with the latter exhibiting superior protective effects. miR-34a-5p effectively mediated Apelin-MSC-EXOs to exert their cardioprotective effects in SMD with high mobility group box-1 (HMGB1) as the potential target. Mechanistically, Apelin-MSC-EXOs delivered miR-34a-5p into injured cardiomyocytes, thereby ameliorating cardiomyocyte pyroptosis via regulation of the HMGB1/AMPK axis. These cardioprotective effects were partially abrogated by downregulation of miR-34a-5p in Apelin-MSC-EXOs.Conclusion: Our study revealed miR-34a-5p as a key component of Apelin-MSC-EXOs that protected against SMD via mediation of the HMGB1/AMPK signaling pathway. Keywords: Exosomes, mesenchymal stem cells, apelin, sepsis-induced myocardial dysfunction, pyroptosis

Objective: To explore the effect and mechanism of human umbilical cord derived-mesenchymal stem cells (UC-MSCs) on improving lipid metabolism disorders in vitro. Methods: Human liver cancer cell line HepG2 cells were divided into three groups: normal group, oleic acid treatment group (OA group), and OA ​+ ​MSCs group. Evaluate lipid deposition in HepG2 cells using oil red staining. Use a reagent kit to detect the triglyceride content in HepG2 cells. Evaluate the mitochondrial transport of MSCs to HepG2 cells using immunofluorescence staining and flow cytometry. Perform immunofluorescence staining to observe the formation of intercellular tunnel nanotubes (TNT). Evaluate the effect of UC-MSCs on HepG2 cells after the formation of TNT was inhibited by cytochalasin D (CytoD). Results: Compared with the OA group, the OA ​+ ​MSCs group showed a decrease in lipid deposition and triglyceride content in HepG2 cells. MitoTracker Red dye was used to label MSCs mitochondria, and flow cytometry showed that over 90 ​% of HepG2 cells had MitoTracker Red positive mitochondria, indicating a significant transfer of mitochondria from UC-MSCs to HepG2 cells. Immunofluorescence staining showed the formation of TNT structures between MSCs and HepG2 cells, and identified the transport of UC-MSCs mitochondria through TNT structures. After inhibiting TNT formation using CytoD, the effect of UC-MSCs on improving HepG2 lipid metabolism was weakened. Conclusion: UC-MSCs improve lipid metabolism in HepG2 cells through TNT mediated mitochondrial transport, indicating that mitochondria transfer-based therapies may be an innovative and promising therapeutic strategy for NAFLD.

Abstract Objective This study aims to explore the potential role of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA), particularly the function of the NOTCH1 signaling pathway in maintaining the stemness of MSCs and in chondrocyte differentiation. Methods Utilizing diverse analytical techniques on an osteoarthritis dataset, we unveil distinct gene expression patterns and regulatory relationships, shedding light on potential mechanisms underlying the disease. Techniques used include the culture of MSCs, induction of differentiation into chondrocytes, establishment of stable cell lines, Western Blot, and immunofluorescence. Through the construction of lentiviruses overexpressing and knocking out NOTCH1, the effects of NOTCH1 on the stemness of MSCs and chondrocyte differentiation were investigated. Additionally, the effects of NOTCH1 on chondrocyte homeostasis and apoptosis were evaluated by adding the EZH2 inhibitor GSK126 and the endoplasmic reticulum stress inducer tunicamycin. Results Experimental results demonstrated that NOTCH1 expression can influence the maintenance of MSC stemness and chondrocyte differentiation by regulating EZH2. Knockout of NOTCH1 decreased the expression of chondrocyte markers, while overexpression increased their expression. Under conditions of endoplasmic reticulum stress, NOTCH1 expression helped reduce the expression of stress-related proteins, maintain chondrocyte homeostasis, and inhibit apoptosis. Conclusion The NOTCH1 signaling pathway plays a crucial role in maintaining the stemness of MSCs, differentiating into chondrocytes, and in the treatment of osteoarthritis. NOTCH1 influences the differentiation fate of MSCs and the homeostasis of chondrocytes by regulating EZH2 and other related genes, offering new targets and strategies for the treatment of diseases like osteoarthritis.

Abstract Background Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model. Method In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized. The mice were treated with MSCs, exosomes, Mesalazine, and a combination of them. Upon sacrificing the mice, colon and spleen tissues were isolated to assess the changes in the mice’s weight, colon length, spleen weight, and colitis’ pathological symptoms. IL-10 and IL-17 levels were measured, and Treg and Th17 cell percentages were determined as well. Furthermore, colon tissue was stained to investigate histopathological changes. Results In the groups that received MSCs, there was a significant reduction in the disease activity index and their combinations with exosomes and Mesalazine compared to the colitis group. Colon length increased in all groups except the exosome group. Histological measures were notably reduced in the MSC groups and their combinations. Significant increases in the IL-10 level of colon tissue and the proportion of Treg present in the spleen were observed in the groups receiving MSC and combination treatment. Furthermore, these groups showed a notable reduction in the percentage of spleen Th17 cells. However, IL17A decreased non-significantly in all groups. Conclusion The results showed that intraperitoneal injection of UC-MSCs and their combination with exosome and Mesalazine in a murine colitis model improved the disease’s symptoms. Therefore, MSCs and their combination with exosomes can be a promising therapeutic approach along with other common drugs for IBD, but exosomes alone could not significantly reduce the symptoms of colitis.

Abstract The prevalence of obesity and osteoporosis (OP) represents a significant public health concern on a global scale. A substantial body of evidence indicates that there is a complex relationship between obesity and OP, with a correlation between the occurrence of OP and obesity. In recent years, sirtuins have emerged as a prominent area of interest in the fields of aging and endocrine metabolism. Among the various research avenues exploring the potential of sirtuins, the effects of these proteins on obesity and OP have garnered significant attention from numerous researchers. Sirtuins regulate energy balance and lipid balance, which in turn inhibit the process of adipogenesis. Additionally, sirtuins regulate the balance between osteogenic and osteoblastic activity, which protects against the development of OP. However, no study has yet provided a comprehensive discussion of the relationship between the three: sirtuins, obesity, and OP. This paper will therefore describe the relationship between sirtuins and obesity, the relationship between sirtuins and OP, and a discussion focusing on the possibility of treating OP caused by obesity by targeting sirtuins. This will be based on the common influences on the occurrence of obesity and OP (such as mesenchymal stem cells, gut microbiota, and insulin). Finally, the potential of SIRT1, an important member of sirtuins, in polyphenolic natural products for the treatment of obesity and OP will be presented. This will contribute to a better understanding of the interactions between sirtuins and obesity and bone, which will facilitate the development of new therapeutic strategies for obesity and OP in the future.

Background: Previous studies revealed diabetes mellitus subjects tend to have persistent apical periodontitis. Regenerative stem cells therapy through endodontic procedure is hoped to be a solution. This study assessed bone regeneration in diabetic rats with apical periodontitis through histopathological analysis of osteoblasts and immunohistochemical analysis of runt-related transcription factor 2 (Runx2) and Osterix. Methods: Diabetes mellitus and apical periodontitis was induced on 20 rats. Apical periodontitis was induced on mandibular right first molars under anesthesia. The teeth were left open for 7 days following access cavity and pulp extirpation, then the rats’ teeth were endodontically treated and randomly allocated into 4 groups (5 rats per group). The first and second groups was ended at 30 days (C30) and 60 days (C60) and labelled as control. The third and fourth groups was given umbilical cord mesenchymal stem cells and ended at 30 days (T30) and 60 days (T60). The osteoblasts, Runx2 and Osterix were analyzed. ANOVA and Tukey HSD tests were used for analysis. Differences with p values

Aims: Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods: In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results: We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion: Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777.

Background: The rat sciatic nerve injury model is one of the most studied models for peripheral nerve injury. Mesenchymal stem cells (MSCs) are known to induce neuroregeneration in this rat model. The most common methods to quantify neuroregeneration in peripheral nerves include histomorphometric analysis of axonal count, length, and mean axonal area. However, histomorphometric analysis remains vague for dorsal root ganglion (DRG). It is known that binucleated neurons (BNs) are present in normal rat populations, increase following the transplantation of bone marrow-derived cells into the cerebellum, and disappear with inflammation. We propose a new potential histologic marker as a probable alternative to conventional axonal histomorphometric analysis for DRG in the Sprague Dawley rat sciatic nerve injury model. Materials and Methods: A total of 32 Sprague Dawley rats were involved in this study, 30 rats were subjected to sciatic chronic constriction injury (CCI) to develop a neuropathic pain model. The rats were randomized into two groups, which received intrathecal normal saline injection (NSI) or stem cell injection (SCI). Human MSCs were intrathecally delivered using ultrasound-guided injection, 7 days after ligation (D7). Samples of DRG were obtained from normal rats (n = 2), from both groups on day 0 (D0), day 14 (D14), and day 28 (D28) post-CCI, analyzing DRG structures of BN. Results: CCI causes neuropathic pain, confirmed using Von Frey at D7, D14, and D28. Histologically, neuroregeneration was observed starting from D14 and D28. Histomorphological analysis revealed BN present exclusively in the SCI group compared with the NSI group. Conclusion: BN may serve as a potential marker for early neuroregeneration in rat sciatic nerve injury models.

Abstract Background Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence. Methods We employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism. Results Here we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix (ECM) function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation. Conclusion Our findings indicate that glutamine-αKG axis may epigenetically promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs and dentin regeneration, which provide a new research vision of potential dental tissue repairment therapy method or metabolite-based drug research.

Abstract Background Radiation-induced heart disease (RIHD) is one of the most serious complications of radiation therapy (RT) for thoracic tumors, and new interventions are needed for its prevention and treatment. Small extracellular vesicles (sEVs) from stem cells have attracted much attention due to their ability to repair injury. However, the role of umbilical cord mesenchymal stem cell (UCMSC)-derived sEVs in protecting cardiac organoids from radiation-induced injury and the underlying mechanisms are largely unknown. Methods A radiation-induced cardiac organoid injury model was established by using X-ray radiation, and the optimal radiation dose of 20 Gy was determined by live/dead staining. After radiation, the cardiac organoids were treated with sEVs derived from UCMSCs, and energy metabolism, calcium transient changes and the ultrastructure of the organoids were assessed through Seahorse analysis, optical mapping and transmission electron microscopy, respectively. Confocal microscopy was used to observe the changes in mitochondrial ROS and mitochondrial membrane potential (ΔΨm). Furthermore, real-time quantitative PCR was used to verify the RNA-seq results. Results After X-ray radiation, the mortality of cardiac organoids significantly increased, energy metabolism decreased, and calcium transients changed. We also observed that the mitochondrial structure of cardiac organoids was disrupted and that ΔΨm was decreased. These effects could be inhibited by sEVs treatment. sEVs may protect against radiation-induced cardiac organoid injury by regulating oxidative phosphorylation and the p53 signaling pathway. Conclusion sEVs derived from UCMSCs can be used as a potential therapeutic strategy for radiation-induced heart disease. Graphical Abstract

Abstract Mesenchymal stem cell (MSC) therapy has been considered a promising approach for the treatment of Parkinson's disease (PD) for several years. PD is a globally prevalent neurodegenerative disease characterized by the accumulation of Lewy bodies and the loss of dopaminergic neurons, leading to severe motor and non-motor complications in patients. As current treatments are unable to halt the progression of neuronal loss and dopamine degradation, MSC therapy has emerged as a highly promising strategy for PD treatment. This promise is due to MSCs' unique properties compared to other types of stem cells, including self-renewal, differentiation potential, immune privilege, secretion of neurotrophic factors, ability to improve damaged tissue, modulation of the immune system, and lack of ethical concerns. MSCs have been employed in numerous pre-clinical and clinical studies for PD treatment with promising results. However, certain aspects of their efficacy in treating PD may benefit from various genetic and epigenetic modifications. In this review article, we assess these approaches to improving MSCs for specialized treatment of PD.

Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a type of interstitial lung disease characterized by chronic inflammation due to persistent lung damage. Mesenchymal stem cells (MSCs), including those derived from the umbilical cord (UCMSCs) and placenta (PLMSCs), have been utilized in clinical trials for IPF treatment. However, the varying therapeutic effectiveness between these two MSC types remains unclear. Methods In this study, we examined the therapeutic differences between UCMSCs and PLMSCs in treating lung damage using a bleomycin (BLM)-induced pulmonary injury mouse model. Results We showed that UCMSCs had a superior therapeutic impact on lung damage compared to PLMSCs. Upon cytokine stimulation, UCMSCs expressed higher levels of inflammation-related genes and more effectively directed macrophage polarization towards the M2 phenotype than PLMSCs, both in vitro and in vivo. Furthermore, UCMSCs showed a preference for expressing CC motif ligation 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1) compared to PLMSCs. The expression of secreted phosphoprotein 1 (SPP1), triggering receptor expressed on myeloid cells 2 (Trem2), and CCAAT enhancer binding protein beta (Cebpb) in macrophages from mice with the disease treated with UCMSCs was significantly reduced compared to those treated with PLMSCs. Conclusions: Therefore, UCMSCs demonstrated superior anti-fibrotic abilities in treating lung damage, potentially through inducing a more robust M2 polarization of macrophages than PLMSCs.

Abstract Background hucMSC-exosomes can be engineered to strengthen their therapeutic potential, and the present study aimed to explore whether hypoxic preconditioning can enhance the angiogenic potential of hucMSC-exosomes in an experimental model of POF. Methods Primary hucMSCs and ROMECs were isolated from fresh tissue samples and assessed through a series of experiments. Exosomes were isolated from hucMSCs under normoxic or hypoxic conditions (norm-Exos and hypo-Exos, respectively) and then characterized using classic experimental methods. Based on a series of angiogenesis-related assays, we found that hypo-Exos significantly promoted ROMEC proliferation, migration, and tube formation and increased angiogenesis-promoting molecules in vitro. Histology, immunohistochemistry, and immunofluorescence experiments in a rat model of POF demonstrated that hypoxia pretreatment strengthens the therapeutic angiogenic effect of hucMSC-exosomes in vivo. Subsequently, high-throughput miRNA sequencing, qRT‑PCR analysis, and western blotting were employed to identify the potential molecular mechanism. Results We found that hypo-Exos enhance endothelial function and angiogenesis via the transfer of miR-205-5p in vitro and in vivo. Finally, based on the results of bioinformatics analysis, dual luciferase reporter assays, and gain- and loss-of-function studies, we found evidence indicating that exosomal miR-205-5p enhances angiogenesis by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. These results indicated for the first time that exosomes derived from hypoxia-conditioned hucMSCs strongly enhance angiogenesis via the transfer of miR-205-5p by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. Conclusions Our findings provide a theoretical basis and demonstrate the potential application of a novel cell-free approach with stem cell-derived products in the treatment of POF.

Abstract Mesenchymal stem cells (MSCs) have shown a great potential role in treating liver injury. MSCs can promote liver regeneration by differentiating into hepatocytes, and can also secrete exosomes to participate in the repair of liver injury. Increasing evidence has shown that mesenchymal stem cell-derived exosomes (MSC-EXOs) play an important role in treating liver injury. In this review, the biogenesis and function of exosomes and the characteristics of MSC-EXOs were analyzed based on recent research results. MSC-EXOs are significant in liver injuries such as liver fibrosis, liver failure, hepatocellular carcinoma, oxidative stress, and lipid steatosis, and participate in the process of liver regeneration.

Abstract Cellular senescence is a phenomenon distinguished by the halting of cellular division, typically triggered by DNA injury or numerous stress-inducing factors. Cellular senescence is implicated in various pathological and physiological processes and is a hallmark of aging. The presence of accumulated senescent cells, whether transiently (acute senescence) or persistently (chronic senescence) plays a dual role in various conditions such as natural kidney aging and different kidney disorders. Elevations in senescent cells and senescence-associated secretory phenotype (SASP) levels correlate with decreased kidney function, kidney ailments, and age-related conditions. Strategies involving senotherapeutic agents like senolytics, senomorphics, and senoinflammation have been devised to specifically target senescent cells. Mesenchymal stem cells (MSCs) and their secreted factors may also offer alternative approaches for anti-senescence interventions. The MSC-derived secretome compromises significant therapeutic benefits in kidney diseases by facilitating tissue repair via anti-inflammatory, anti-fibrosis, anti-apoptotic, and pro-angiogenesis effects, thereby improving kidney function and mitigating disease progression. Moreover, by promoting the clearance of senescent cells or modulating their secretory profiles, MSCs could potentially reverse some age-related declines in kidney function. This review article intends to shed light on the present discoveries concerning the role of cellular senescence in kidney aging and diseases. Furthermore, it outlines the role of senotherapeutics utilized to alleviate kidney damage and aging. It also highlights the possible impact of MSCs secretome on mitigating kidney injury and prolonging lifespan across various models of kidney diseases as a novel senotherapy.

Cellular heterogeneity, an inherent feature of biological systems, plays a critical role in processes such as development, immune response, and disease progression. Human mesenchymal stem cells (hMSCs) exemplify this heterogeneity due to their multi-lineage differentiation potential. However, their inherent variability complicates clinical use, and there is no universally accepted method for detecting and quantifying cell population heterogeneity. Dielectrophoresis (DEP) has emerged as a powerful electrokinetic technique for characterizing and manipulating cells based on their dielectric properties, offering label-free analysis capabilities. Quantitative information from the DEP spectrum, such as transient slope, measure cells’ transition between negative and positive DEP behaviors. In this study, we employed DEP to estimate transient slope of various cell populations, including relatively homogeneous HEK-293 cells, heterogeneous hMSCs, and cancer cells (PC3 and DU145). Our analysis encompassed hMSCs derived from bone marrow, adipose, and umbilical cord tissue, to capture tissue-specific heterogeneity. Transient slope was assessed using two methods, involving linear trendline fitting to different low-frequency regions of the DEP spectrum. We found that transient slope serves as a reliable indicator of cell population heterogeneity, with more heterogeneous populations exhibiting lower transient slopes and higher standard deviations. Validation using cell morphology, size, and stemness further supported the utility of transient slope as a heterogeneity metric. This label-free approach holds promise for advancing cell sorting, biomanufacturing, and personalized medicine.

Abstract Background Native cartilage has low capacity for regeneration because it has very few progenitor cells. Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs) and human umbilical cord‐derived MSCs (hUC‐MSCs) have been employed as promising sources of stem cells for cartilage injury repair. Reproduction of hyaline cartilage from MSCs remains a challenging endeavor. The paracrine factors secreted by chondrocytes possess the capability to induce chondrogenesis from MSCs. Methods The conditioned medium derived from chondrocytes was utilized to induce chondrogenic differentiation of hUCB‐MSCs and hUC‐MSCs. The expression levels of collagen type I alpha 1 chain (Col1a1), collagen type II alpha 1 chain (Col2a1), and SRY‐box transcription factor 9 (SOX9) were assessed through quantitative real‐time polymerase chain reaction (qRT‐PCR), Western blot (WB), and immunofluorescence (IF) assays. To elucidate the mechanism of differentiation, the concentration of transforming growth factor‐β1 (TGF‐β1) in the conditioned medium of chondrocytes was quantified using enzyme‐linked immunosorbent assay (ELISA). Meanwhile, the viability of cells was assessed using Cell Counting Kit‐8 (CCK‐8) assays. Results The expression levels of Col2a1 and SOX9 were found to be higher in induced hUC‐MSCs compared to those in induced hUCB‐MSCs. The conditioned medium of chondrocytes contained TGF‐β1. The CCK‐8 assays revealed that the proliferation rate of hUC‐MSCs was significantly higher compared to that of hUCB‐MSCs. Conclusions The chondrogenic potential and proliferation capacity of hUC‐MSCs surpass those of hUCB‐MSCs, thereby establishing hUC‐MSCs as a superior source of seed cells for cartilage tissue engineering.

Abstract Mycobacterium tuberculosis (M. tb) has a remarkable ability to persist inside host cells. Several studies showed that M. tb infects and survives inside bone marrow mesenchymal stem cells (BM-MSCs) escaping the host immune system. Here, we have identified various cellular pathways that are modulated in human BM-MSCs upon infection with virulent M. tb and the proteomic profile of these cells varies from that of avirulent M. tb infected cells. We found that virulent M. tb infection reshapes host pathways such as stem cell differentiation, alternative splicing, cytokine production, mitochondrial function etc., which might be modulated by M. tb to persist inside this unconventional niche of human BM-MSCs. Additionally, we observed that virulent M. tb infection suppresses various cellular processes. This study uncovers the differences in the host proteomic profiles resulting from the virulent versus avirulent M. tb infection that can pave the way to identify host-directed therapeutic targets for the treatment of tuberculosis.

Abstract Background Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects. Methods Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats. Results In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery. Conclusions Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects. Graphical abstract

Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/β-catenin signalling pathway activation via deubiquitination of β-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway.

Sahar AlOraibi, Sebastien Taurin, Sfoug Alshammary Molecular Medicine Department, Princess Al Jawhara Center for Molecular Medicine, Genetics, and Hereditary Diseases, College of Medicine and Health Sciences, Arabian Gulf University, Manama, BahrainCorrespondence: Sfoug Alshammary, Arabian Gulf University, Building 293, Road 2904, Manama, Bahrain, Tel +973 17237336, Email sfoug1@gmail.comAbstract: Biobanking has emerged as a transformative concept in advancing the medical field, particularly with the exponential growth of umbilical cord (UC) biobanking in recent decades. UC blood and tissue provide a rich source of primitive hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) for clinical transplantation, offering distinct advantages over alternative adult stem cell sources. However, to fully realize the therapeutic potential of UC-derived stem cells and establish a comprehensive global UC-biobanking network, it is imperative to optimize and standardize UC processing, cryopreservation methods, quality control protocols, and regulatory frameworks, alongside developing effective consent provisions. This review aims to comprehensively explore recent advancements in UC biobanking, focusing on the establishment of rigorous safety and quality control procedures, the standardization of biobanking operations, and the optimization and automation of UC processing and cryopreservation techniques. Additionally, the review examines the expanded clinical applications of UC stem cells, addresses the challenges associated with umbilical cord biobanking and UC-derived stem cell therapies, and discusses the promising role of artificial intelligence (AI) in enhancing various operational aspects of biobanking, streamlining data processing, and improving data analysis accuracy while ensuring compliance with safety and quality standards. By addressing these critical areas, this review seeks to provide insights into the future direction of UC biobanking and its potential to significantly impact regenerative medicine.Keywords: umbilical cord biobanking, hematopoietic stem cells, mesenchymal stem cells, cryopreservation, artificial intelligence

Abstract Background Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis. Results Sepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival. Conclusions Treatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis.

Abstract Background/aims Mesenchymal stem cells (MSCs) have shown promising therapeutic potential in treating liver diseases, such as non-alcoholic fatty liver disease (NAFLD). Genetic modification has been employed to enhance the characteristics of MSCs for more effective disease treatment. Here, we present findings on human adipose-derived MSCs with Atg5 deficiency, investigating their therapeutic impact and the associated mechanisms in NAFLD. Methods In vitro, lentiviral transduction was employed to downregulate Atg5 or HGF in human adipose-derived MSCs using short hairpin RNA (shRNA). Subsequently, experiments were conducted to evaluate cell senescence, proliferation, cell cycle, apoptosis, and other pertinent aspects. In vivo, a non-alcoholic fatty liver mouse model was established by feeding them a high-fat diet (HFD), and the effects of MSCs transplantation were assessed through serological, biochemical, and pathological analyses. Results Our research findings indicate that Atg5-deficient MSCs display heightened proliferative activity. Subsequent co-culturing of MSCs with hepatocytes and the transplantation of Atg5-deficient MSCs into NAFLD mouse models demonstrated their ability to effectively reduce lipid accumulation in the NAFLD disease model by modulating the AMPKα/mTOR/S6K/Srebp1 pathway. Furthermore, we observed that Atg5 deficiency enhances the secretion of hepatocyte growth factor (HGF) by promoting recycling endosome (RE) production. Lastly, our study revealed that 3-MA-primed MSCs can improve the characteristics of NAFLD by boosting the secretion of HGF. Conclusions Our research findings suggest that Atg5-deficient MSCs protect against NAFLD by accelerating HGF secretion. This indicates that Atg5 gene-modified MSCs may represent a promising strategy for treating NAFLD.

Magnesium (Mg)-based implants have emerged as a promising alternative for orthopedic applications, owing to their bioactive properties and biodegradability. As the implants degrade, Mg2+ ions are released, influencing all surrounding cell types, especially mesenchymal stem cells (MSCs). MSCs are vital for bone tissue regeneration, therefore, it is essential to understand their molecular response to Mg2+ ions in order to maximize the potential of Mg-based biomaterials. In this study, we conducted a gene regulatory network (GRN) analysis to examine the molecular responses of MSCs to Mg2+ ions. We used time-series proteomics data collected at 11 time points across a 21-day period for the GRN construction. We studied the impact of Mg2+ ions on the resulting networks and identified the key proteins and protein interactions affected by the application of Mg2+ ions. Our analysis highlights MYL1, MDH2, GLS, and TRIM28 as the primary targets of Mg2+ ions in the response of MSCs during 1–21 days phase. Our results also identify MDH2-MYL1, MDH2-RPS26, TRIM28-AK1, TRIM28-SOD2, and GLS-AK1 as the critical protein relationships affected by Mg2+ ions. By offering a comprehensive understanding of the regulatory role of Mg2+ ions on MSCs, our study contributes valuable insights into the molecular response of MSCs to Mg-based materials, thereby facilitating the development of innovative therapeutic strategies for orthopedic applications.

Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs. They can be caused by ischemic factors or hemorrhages, with ischemic strokes being the most common among the population. Therapies for patients suffering from this condition are limited and primarily focus on acute-phase treatment. In recent years, there has been an increase in cellular therapies, employing Stem Cells to mitigate or eliminate the consequences arising from this disease. Mesenchymal Stem Cells (MSCs) hold substantial therapeutic potential in Nervous System pathologies due to their low antigenicity and capacity to differentiate into various human tissues, such as adipogenic, chondrogenic, and osteogenic tissues. This study conducts a literature review using the “clinical trials” and “Pubmed” database, summarizing all ongoing clinical trials for ischemic strokes that utilize MSCs as treatment.

The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.

Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFβ-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFβ-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs were isolated from six healthy horses and exposed to TGFβ-1 for 4, 24, and 0 h. The expression of anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles was measured. The resulting EVs were added for 48 h to endometrial stromal cells previously induced to a fibrotic status. The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was evaluated in said cells using qPCR and next-generation sequencing. Preconditioning MSCs with TGFβ-1 for 4 h enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs. Conversely, preconditioning the cells for 24 h leads to a pro-fibrotic phenotype overexpressing mir192 and mir433. This finding might have implications for developing an EV-based protocol to treat endometrial fibrosis in mares.

Platelet lysate, derived from platelets, are valuable biological products rich in bioactive molecules. Their use promotes tissue healing and modulates inflammation. However, maintaining the stability and bioactivity of platelet lysate is challenging since they degrade rapidly at room temperature. This study focused on the possibility to confer enhanced stability to freeze-dried equine platelet lysate as an alternative to platelet-rich plasma (PRP). Platelet lysate (PL) was derived from PRP and freeze-dried either as such or using various adjuvants. Primary cell cultures of porcine Vascular Wall-Mesenchymal Stem Cells were treated with different PL formulations, and cell viability was assessed using an MTT assay. Overall, the addition of PL significantly improved cell viability as compared to controls without growth factor supplementation or with foetal bovine serum. Notably, the freeze-drying process maintained the effectiveness of the PL for at least a week. Furthermore, the study revealed that varying the horse as the source of PL could yield varying effects on cell viability. Detailed freeze-drying protocols were established, including freezing, primary drying and secondary drying phases, and the type of adjuvant. This study demonstrated the potential of freeze-dried equine PL as a viable alternative to PRP and highlighted the importance of precise freeze-drying protocols and adjuvants for standardization. Equine PL showed promise for medical treatment in horses, offering advantages such as extended shelf life, ease of handling, and reduced transportation costs, with the potential for broadened therapeutic usage.

Abstract Background Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue‐derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor‐α (TNF‐α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp‐derived MSCs obtained from T2DM individuals (dDPMSCs). Methods dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF‐α, and (c) induction cocktail+ TNF‐α + ADMSCs‐secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse‐transcription polymerase chain reaction (RT‐PCR). Results Treatment of TNF‐α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, p

INTRODUCTION. Cell therapies and tissue-engineered products are aimed at patients with severe conditions (genetic and neurodegenerative disorders, cancers, musculoskeletal injuries, burns, etc.) that lack alternative treatment options. Analysis of clinical efficacy data on cell-based medicinal products is important for understanding their translational potential in personalised medicine.AIM. This study aimed to review key trends in cell therapy, analyse data on approved cell therapies and tissue-engineered products, and assess challenges and prospects for their use.DISCUSSION. This article analyses data on the composition of cell therapies and tissue-engi­neered products, indications for their use, and the results of clinical studies. Cell-based medicinal products are derived from autologous or allogeneic mesenchymal and limbal stem cells, epithelial cells, chondrocytes, native or genetically engineered haematopoietic stem cells, geneti­cally engineered lymphocytes (CAR-T, CAR-NK), etc. Medicinal products based on cell technologies have been approved in many countries, including the USA (approximately 30), the European Union (approximately 20), Japan (18), South Korea (15), etc. As of today, two cell therapies have been granted marketing authorisation in the Russian Federation. The first is based on CAR-T cells (a gene therapy product), and the other is based on chondrocytes (a cell-based medicinal product); the latter has been developed in Russia. The main advantages of cell therapy products include higher efficacy and fewer adverse drug reactions in comparison with standard treatment modalities. The main challenges of cell therapy include the risks of immune reactions and mutagenesis associated with lentiviral vectors or CRISPR/Cas9 technology, as well as limited efficacy of CAR-T and CAR-NK cells due to immunosuppressive properties of tumour microenvironment.CONCLUSION. In comparison with conventional treatment approaches, the use of cell therapies and tissue-engineered products can help effectively eliminate defects in various body tissues, avoid highly invasive surgical interventions, and reduce regeneration time. Thus, ensuring development of similar but at the same time more affordable Russian medicinal products can bring great benefits for the healthcare system of the Russian Federation.

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co2+ and Co3+, namely STCh that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co2+ and Co3+ locate at TiO6 octahedral interlayers and within octahedra of STCh lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co3+/Co2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STCh-regulated MΦs, in combination with the released Co2+, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co2+and ST. STCh array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood–brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

Stem cells are crucial for maintaining bodily stability, but their regenerative abilities decline with age. This decline is marked by reduced proliferation and differentiation capacities of stem cells, as well as exhaustion of the stem cell pool. The accumulation of aged mesenchymal stem cells (MSCs) can reduce the tissue regeneration, but the molecular mechanisms influencing MSCs aging remain unclear. Moreover, collecting MSCs from elderly individuals is not suitable for observing the early response of MSCs to senescence stress, and the factors involved in early senescence remain unclear. In our previous study, we established a fast MSC aging model using D-galactose. We discovered that, while not affecting the ''stemness'' markers of mesenchymal stem cells, the expression of LncRNA NEAT1-206 was notably increased during the early stages of aging induction (within 4 days). And LncRNA NEAT1-206 was observed to be localized in the cytoplasmic matrix due to enhanced nuclear export. We found that the LncRNA NEAT1-206 could trigger autophagy through the WNT5A/Ca2+ signaling pathway, thereby decreasing senescence markers and enhancing the osteogenic differentiation of MSCs. This study elucidated the role that LncRNA NEAT1-206 as a potential key factor in conferring resistance to D-galactose-induced cell senescence at the early stage and promoting the osteogenic differentiation of MSCs. This study may provide a foundational understanding for delaying the MSCs aging process.

Our previous studies have reported that activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been shown to restore the neuroinflammatory response, along with myelin and synaptic structural alterations in the prefrontal cortex, and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice. Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles, the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue, which inhibited the activation of the NLRP3 inflammasome, was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., pyrin domain-containing 1, caspase recruitment domain-containing 4, and absent in melanoma 2, as well as the alterations in inflammatory genes (interleukin-1β, interleukin-18, inducible nitric oxide synthase, nuclear factor-kappa B, monocyte chemoattractant protein-1, and C–X3–C motif chemokine ligand 1) and miRNAs (miR-21a-5p, miR-146a-5p, and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology. Originally identified as a key regulator of heart development and specification, GATA4 has since been connected to several aspects of cellular processes, including stem cell proliferation and differentiation. Accumulating evidence suggests that the involvement of GATA4-nuclear signalizing in the process of MSC senescence-related traits may contribute to age-induced alterations in MSC behavior. GATA4 emerged as the central player in MSC senescence, interacting with several signaling pathways. Studies have shown that GATA4 expression is reduced with age in MSCs, which is associated with increased expression levels of senescence markers and impaired regenerative potential. At the mechanistic level, GATA4 regulates the expression of genes involved in cell cycle regulation, DNA repair, and oxidative stress response, thereby influencing the senescence phenotype in MSCs. The findings underscore the critical function of GATA4 in MSC homeostasis and suggest a promising new target to restore stem cell function during aging and disease. A better understanding of the molecular mechanisms that underlie GATA4 mediated modulation of MSC senescence would provide an opportunity to develop new therapies to revitalize old MSCs to increase their regenerative function for therapeutic purposes in regenerative medicine.

Background: Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms. Methods: A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSCIronQ). Renal function, histology, and tubular cell apoptosis were analyzed three days post-treatment. In vitro, apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSCIronQ conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA sequencing (RNA-seq) was performed on MSCIronQ to explore the underlying mechanisms. Results: Compared to MSC-treated AKI mice, those treated with MSCIronQ showed significantly improved renal function and histological outcomes, with reduced tubular cell apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSCIronQ-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSCIronQ on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models. Conclusions: IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.

Peripheral nerve damage continues to be a significant challenge in the field of medicine, with no currently available effective treatment. Currently, we investigated the beneficial effects of human placenta mesenchymal stem cells (PMSCs)- derived exosomes along with hyperbaric oxygen therapy (HBOT) in a sciatic nerve injury model. Seventy-five male mature Sprague-Dawley rats were allocated into five equal groups. In addition to the control group that received no intervention, damaged animals were allocated into four groups as follows: crush group, exosome group, HBOT group, and Exo+HBOT group. After the last neurological evaluations, tissue samples (sciatic nerve and dorsal root ganglion (DRG)) at the injury side, as well as spinal cord segments related to the sciatic nerve were collected to investigate histological, immunohistochemical, biochemical, and molecular characteristics. We found that the volume of the sciatic nerve, the thickness of the myelin sheath, the densities of nerve fibers and Schwann cells, the numerical densities of sensory neurons and glial cells in the DRG, as well as the numerical density of motor neurons in the anterior horn of the spinal cord, the levels of antioxidative factors (GSH, SOD, and CAT) in the sciatic nerve, as well as the neurological functions (EMG latency and SFI) in the treatment groups, especially the Exo+HBOT group, were significantly improved compared to the crush group. This is while the numerical density of glial cells in the spinal cord, the levels of an oxidative factor (MDA), and pro-inflammatory cytokines (IL-1β, TNF-α, and IFN- γ) considerably decreased in the treatment groups, particularly the Exo+HBOT group, compared to the crush group. We conclude that co-administration of PMSCs-derived exosomes and HBOT has synergistic neuroprotective effects in animals undergoing sciatic nerve injury.

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the accumulation of abnormal plasma cells in the bone marrow. Mesenchymal stem cells (MSCs) and reticulated platelets (RPs) have been implicated in the pathogenesis of MM. This narrative review aims to explore the role of MSCs and RPs in the pathophysiology of MM, particularly their clinical use as possible variables of prognostic value in this hematologic neoplasia. The interaction between MSCs and MM cells within the bone marrow microenvironment supports MM cell survival, proliferation, and drug resistance. MSCs contribute to the development and maintenance of MM through the secretion of various factors, including cytokines, chemokines, and growth factors. Moreover, RPs, young and highly reactive platelets, have been implicated in promoting angiogenesis, tumor growth, and metastasis in MM. Several studies show that cells such as MSCs and platelets participate actively in the biology of the disease. Still, in clinical practice, they are not considered part of evaluating affected patients. In this review, we explore the possibility of including the evaluation of MSCs and PRs in the clinical practice for patients with MM as part of the strategies to improve the outcomes of this disease.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells present in adult tissues that are recognized as promising candidates for cell therapy due to their ease of access, straightforward isolation, and capacity for bio-preservation with minimal loss of potency. However, the clinical application of MSCs faces significant challenges, such as donor site morbidity, underscoring the need for alternative sources. Recent studies have suggested that inferior turbinate tissues, which are commonly removed during turbinate surgery, may be a viable donor site for MSCs. Turbinate surgery is a safe and effective procedure frequently performed to alleviate nasal obstruction, a prevalent chronic condition treated by otolaryngologists. This implies that harvesting MSCs from turbinate tissue for tissue engineering and regenerative medicine could serve as a simple, minimally invasive method with faster healing and minimal risk of morbidity or scarring at the donor site. This review highlights previous research indicating that MSCs derived from human turbinate tissues maintain their stability and demonstrate multi-differentiation potential. Therefore, the turbinate could be an alternative to traditional MSC sources for producing functionally competent cells for future clinical applications.