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Myocardial infarction (MI) is a leading cause of heart failure, disability and mortality worldwide. In this study, the effects of intramyocardial injection of human platelet lysate (HPL), bone marrow mesenchymal stem cells pretreated with HPL (PMSCs), and PMSC lysate (lys), alone and in combination were investigated on MI-induced by LAD ligation in male Wistar rats. The experiment was carried out on sham, vehicle (Veh), HPL, PMSCs, PMSC lysate (PMSC lys), HPL + PMSCs, and HPL + PMSC lys groups. SBP, DBP, and ± dp/dt max were monitored by the PowerLab physiograph. The MSC characteristics and CD31, NKX2.5, and cardiac troponin I (cTnI) contents were determined by flow cytometry, immunohistochemistry, and immunofluorescence, respectively. SBP, DBP, and ± dp/dt max that decreased in the MI group were recovered by HPL, PMSC, PMSC lys, HPL + PMSC, and HPL + PMSC lys treatments. CD31 density was higher in all treated groups compared to the Veh group. CD31 density in the HPL + PMSCs and HPL + PMSC lys groups was higher than in the PMSCs group. The number of Dil+/NKX2.5 + and Dil+/cTnI + cells was higher in the HPL + PMSCs group compared to the PMSCs group. The HPL and PMSCs mitigates heart injuries and cardiac dysfunction after MI. HPL provides an appropriate environment for cardiomyocyte differentiation from PMSCs. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a leading cause of heart failure, disability and mortality worldwide. In this study, the effects of intramyocardial injection of human platelet lysate (HPL), bone marrow mesenchymal stem cells pretreated with HPL (PMSCs), and PMSC lysate (lys), alone and in combination were investigated on MI-induced by LAD ligation in male Wistar rats. The experiment was carried out on sham, vehicle (Veh), HPL, PMSCs, PMSC lysate (PMSC lys), HPL + PMSCs, and HPL + PMSC lys groups. SBP, DBP, and ± dp/dt max were monitored by the PowerLab physiograph. The MSC characteristics and CD31, NKX2.5, and cardiac troponin I (cTnI) contents were determined by flow cytometry, immunohistochemistry, and immunofluorescence, respectively. SBP, DBP, and ± dp/dt max that decreased in the MI group were recovered by HPL, PMSC, PMSC lys, HPL + PMSC, and HPL + PMSC lys treatments. CD31 density was higher in all treated groups compared to the Veh group. CD31 density in the HPL + PMSCs and HPL + PMSC lys groups was higher than in the PMSCs group. The number of Dil+/NKX2.5 + and Dil+/cTnI + cells was higher in the HPL + PMSCs group compared to the PMSCs group. The HPL and PMSCs mitigates heart injuries and cardiac dysfunction after MI. HPL provides an appropriate environment for cardiomyocyte differentiation from PMSCs. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative joint condition characterised by cartilage deterioration and changes in bone morphology, resulting in pain and impaired joint mobility. Investigation into the pathophysiological mechanisms underlying OA has highlighted the significance of mitochondrial dysfunction in its progression. Mitochondria, which are cellular organelles, play a crucial role in regulating energy metabolism, generating reactive oxygen species, and facilitating essential biological processes including apoptosis. In recent years, the utilisation of exogenous drugs and MT to improve mitochondrial function in chondrocytes has shown great promise in OA treatment. Numerous studies have investigated the potential of stem cells and extracellular vesicles in mitochondrial transfer. This review aims to explore the underlying mechanisms of mitochondrial dysfunction in OA and assess the progress in utilising mitochondrial transfer as a therapeutic approach for this disease. [ABSTRACT FROM AUTHOR]

Bone marrow stem cells (BMSCs)‐engineered cartilage (BEC) shows promise for clinically repairing cartilage defects. However, when implanted in immunocompetent large animals, BEC becomes susceptible to ossification due to inflammatory infiltration. To address this, a nanofilm isolation approach is developed to enhance BEC's chondrogenic stability. Tacrolimus (FK506), known for its immunosuppressive effect, is integrated into adipic dihydrazide (ADH)‐modified hyaluronic acid (HA), creating an acid‐responsive macromolecular prodrug called FK506@HA‐ADH. This prodrug is then blended with poly(lactic‐co‐glycolic acid) (PLGA) to form electrospun FK506@HA/PLGA nanofilm. Goat‐derived BMSCs are induced in vitro to form BEC, which is enclosed within the FK506@HA/PLGA nanofilm and subcutaneously implanted in autologous goats. The nanofilm acted as a physical barrier, preventing immunocyte infiltration. Additionally, in response to the acidic environment triggered by inflammation and the gradual degradation of PLGA, the FK506@HA‐ADH prodrug is cleaved, releasing FK506 as needed. The released FK506 effectively countered inflammatory cytokines and promoted cartilaginous maturity. These combined mechanisms significantly inhibited BEC hypertrophy and improved its chondrogenic stability within an immunocompetent goat model. This nanofilm‐based isolation strategy established an immunosuppressive niche, successfully preventing endochondral ossification and promoting stable cartilage formation in BEC. These advancements are crucial for translating stem cell‐based therapies into clinical use for cartilage repair. [ABSTRACT FROM AUTHOR]

Cellular biomechanical features contributed to the occurrence and development of various physiological and pathological phenomena. Micropillar arrays have emerged as an important tool for both the assessment and manipulation of cellular biomechanical characteristics. This comprehensive review provides an in-depth understanding of the fabrication methodologies of micropillar arrays and their applications in deciphering and fine-tuning cellular biomechanical properties and the innovative experimental platforms including organ-on-a-chip and organoids-on-a-chip. This review provides novel insights into the potential of micropillar technology, poised to update the landscape of stem cell research and tissue engineering. [ABSTRACT FROM AUTHOR]

Stem cells have shown great application potential in wound repair, tissue regeneration, and disease treatment. Therefore, a full understanding of stem cells and their related regulatory mechanisms in disease treatment is conducive to improving the therapeutic effect of stem cells. However, thus far, there are still many unsolved mysteries in the field of stem cells due to technical limitations, which hinder the in-depth exploration of stem cells and their wide clinical application. Single-cell sequencing (SCS) has provided very powerful and unbiased insights into cell gene expression profiles at the single-cell level, bringing exciting results to the stem cell field. At present, SCS has been widely applied in the field of stem cells, covering various aspects, including lineage tracing the development of stem cells, identifying new stem cell types, exploring cellular heterogeneity, and identifying internal functional subpopulations. In this paper, we focus on the latest research progress and discuss the application of SCS technology in stem cells. [ABSTRACT FROM AUTHOR]

This study evaluated the role of the mesenchymal stem cells derived from adipose tissue (MSCs) in provoked ventricular arrhythmias (VAs) in animals with myocardial infarction (MI). The experimental groups were: sham, subjected to sham surgery and intramyocardial saline injection; MIV, infarcted rats subjected to intramyocardial saline injection; MI + MSCs, infarcted rats subjected to intramyocardial MSCs injection. Injections were performed two days after infarction and the arrhythmogenic inducibility experiment was performed the next day. Only 35% of the MI + MSCs group developed VAs, while the one in the MIV group was 65%. The proportion of nonsustained ventricular tachycardia, sustained tachycardia, and ventricular fibrillation was similar between the infarcted groups, but MSCs animals had shorter duration of nonsustained ventricular tachycardia. However, MSCs increased connexin 43 content in the remote area, even above the levels found in the sham group. MSCs prevented the increase of IL-1β in the different areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of infarcted rats, but MSCs attenuated the increase of 4-HNE in the infarcted area. In conclusion, MSCs have a protective effect against the development of arrhythmias, but do not imply a significant benefit for animals that have developed VAs. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidative actions and improvement in the formation of communicating junctions. Graphical abstract [ABSTRACT FROM AUTHOR]

This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. Five rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6–8.8]), control (6.7 [5.9–7.6]), and early excision (7.5 [6.6–8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5–16.9]) had the highest TOC levels. The PLM group (9.7 [8.6–10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10–30]), early excision group (25 [15–50]), PLM group (70 [50–100]), control group (0), and burn group (80 [60–120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results. • Systemic inflammation and oxidative stress occur during the acute phase of severe burns, causing damage to end organs. • Wound healing is an important problem in patients with severe burns if there is not enough space to harvest the skin autograft. • Early excision treatment, which involves clearing local necrotic tissue after extensive and deep severe burns, can prevent end-organ damage. • The stem cells may have the potential to form new skin and its appendages providing better healing for large skin defects. • Combining these two treatments may yield the best results. [ABSTRACT FROM AUTHOR]

In this review we discuss how the mammalian interfollicular epidermis forms during development, maintains homeostasis, and is repaired following wounding. Recent studies have provided new insights into the relationship between the stem cell compartment and the differentiating cell layers; the ability of differentiated cells to dedifferentiate into stem cells; and the epigenetic memory of epidermal cells following wounding. [Display omitted] • Switch between planar and perpendicular cell divisions during development. • Epidermal signalling is integrated at the cellular and supracellular levels. • Epigenetic environmental and lineage memory of wounding. [ABSTRACT FROM AUTHOR]

Perianal fistulizing Crohn's disease (CD) is a severe gastrointestinal disorder causing extensive mucosal damage with limited treatment options. Severe manifestations of the disease appear at higher rates in non-Europeans but the genetic and cellular mechanisms driving the disease phenotypes remain poorly understood. Herein, we tested whether pathologic determinants in the epithelial stem cell compartment could be detected at the transcript level in rectal organoids derived from a diverse patient population. Rectal organoid and mucosal cells from endoscopic biopsies of each patient having perianal fistulizing CD or no disease controls were prepared for and sequenced at the single cell level. After cell type annotations based on expressed marker genes, samples were analyzed by principal components, for differential transcript expression, cell type proportions, and pathway enrichment. After QC, we produced 77,044 rectal organoid cells (n = 13 patients; 8 CD, 5 controls) with high quality sequences that identified 10 distinct epithelial subtypes, that we compared to 141,367 mucosal epithelial cells (n = 29 patients; 18 CD, 11 controls). Consistent with mucosal epithelial cells, rectal organoids prominently displayed disease signatures represented by the stem and transit amplifying regions of the rectal crypt, including alterations in transcriptional signatures of metabolic, epigenetic, and proliferating pathways. Organoids also retained their gender- and ancestral-specific gene expression signatures. However, they lacked many of the inflammatory signatures observed in epithelial cells from diseased mucosa. Perianal CD patient derived rectal organoids reflect gene expression signatures related to disease, gender, and ancestry, suggesting they harbor inherent properties amenable to further patient-specific, disease-related experimentation. [ABSTRACT FROM AUTHOR]

AbstractBackgroundAim/objectivesMaterial and MethodsResultsConclusionsHematopoietic stem cell transplantation (HSCT) is a critical treatment for various hematologic malignancies but can lead to complications, including ototoxicity.This study aims to explore the relationship between patient-specific factors and ototoxicity in adult HSCT patients.We conducted a retrospective analysis of 129 adult patients who underwent HSCT between 2003 and 2020. Age, gender, transplant indications, conditioning regimens, and pre- and post-transplant audiometry thresholds data were collected from patient files. A hearing loss of 10 decibels or more at two consecutive frequencies or a hearing loss of 20 decibels or more at a single frequency was considered as significant hearing loss (SHL). Statistical analyses were performed to describe factors associated with SHL.SHL occurred in 16.3% of patients. Older age was significantly associated with an increased risk of SHL (p = .035). Poorer pretransplant hearing thresholds at 4000 Hz and 6000 Hz were also significant predictors of SHL (p = .039 and p = .014, respectively). There was no significant relationship between the donor type of HSCT (autologous vs. allogeneic) and ototoxicity (p = .45), and between conditioning regimens and ototoxicity (p = .860).Age and pre-existing hearing levels are significant predictors of ototoxicity post-HSCT. Careful management and monitoring are essential to prevent and address hearing loss in HSCT patients to improve hearing-related quality of life. [ABSTRACT FROM AUTHOR]

Wound healing comprises an intricate process to repair damaged tissue. Research on plant extracts with properties to expedite wound healing has been of interest, particularly their ability to enhance the stemness of keratinocyte stem cells. Hence, the present study aims to determine the wound healing and stemness potentiation properties of an ethanolic extract derived from Cucurbita moschata fruit pulp (PKE). Human keratinocytes (HaCaT) and primary skin fibroblast cells were used in this study. The migration of the cells was examined by using a scratch wound healing assay, and spheroid behavior was determined by using a spheroid formation assay. The proteins related to migration and stemness were further measured by using Western blotting to explore the mechanism of action of PKE. The methods used to evaluate PKE's antioxidant properties were 2,2‐diphenyl‐2‐picrylhydrazyl (DPPH) scavenging, ABTS radical scavenging activity, and superoxide anion radical scavenging (SOSA) assays. The phytochemistry of the PKE was investigated using phytochemical screening and high‐performance liquid chromatography (HPLC) analysis. The results of this study indicate that nontoxic concentrations of PKE increase the rate of migration and spheroid formation. Mechanistically, PKE increased the expression of the migratory‐related protein active FAK (phosphorylated FAK), and the subsequence increased the level of p‐AKT. The expression of stem cell marker CD133, upstream protein signaling β‐catenin, and self‐renewal transcription factor Nanog was increased. The PKE also possessed scavenging properties against DPPH, ABTS, and SOSA. The phytochemistry analyses exhibited the presence of alkaloids, glycosides, xanthones, triterpenes, and steroids. Additionally, bioactive compounds such as ɑ‐tocopherol, riboflavin, protocatechuic acid, β‐carotene, and luteolin were detected. The presence of these chemicals in PKE may contribute to its antioxidant, stem cell potentiation, and wound‐healing effects. The findings could be beneficial in the identification of valuable natural resources that possess the capacity to be used in the process of wound healing through the potentiation of stemness via a readily detectable molecular mechanism. [ABSTRACT FROM AUTHOR]

Background: Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections. Methods: We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion. Results: From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research. Conclusions: Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications. [ABSTRACT FROM AUTHOR]

Sea urchins are basal deuterostomes that share key molecular components of innate immunity with vertebrates. They are a powerful model for the study of innate immune system evolution and function, especially during early development. Here we characterize the morphology and associated molecular markers of larval immune cell types in a newly developed model sea urchin, Lytechinus pictus. We then challenge larvae through infection with an established pathogenic Vibrio and characterize phenotypic and molecular responses. We contrast these to the previously described immune responses of the purple sea urchin Strongylocentrotus purpuratus. The results revealed shared cellular morphologies and homologs of known pigment cell immunocyte markers (PKS, srcr142) but a striking absence of subsets of perforin‐like macpf genes in blastocoelar cell immunocytes. We also identified novel patterning of cells expressing a scavenger receptor cysteine rich (SRCR) gene in the coelomic pouches of the larva (the embryonic stem cell niche). The SRCR signal becomes further enriched in both pouches in response to bacterial infection. Collectively, these results provide a foundation for the study of immune responses in L. pictus. The characterization of the larval immune system of this rapidly developing and genetically enabled sea urchin species will facilitate more sophisticated studies of innate immunity and the crosstalk between the immune system and development. [ABSTRACT FROM AUTHOR]

CD133 protein expression is observable in differentiated cells, stem cells, and progenitor cells within normal tissues, as well as in tumor tissues, including colorectal cancer cells. The CD133 protein is the predominant cell surface marker utilized to detect cancer cells exhibiting stem cell-like characteristics. CD133 alters common abnormal processes in colorectal cancer, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin pathways. Autophagy is a cellular self-digestion mechanism that preserves the intracellular milieu and plays a dual regulatory role in cancer. In cancer cells, apoptosis is a critical cell death mechanism that can impede cancer progression. CD133 can modulate autophagy and apoptosis in colorectal cancer cells via several signaling pathways; hence, it is involved in the regulation of these intricate processes. This can be an explanation for why CD133 expression is associated with enhanced cellular self-renewal, migration, invasion, and survival under stress conditions in colorectal cancer. The purpose of this review article is to explain the complex relationship between the CD133 protein, apoptosis, and autophagy. We also want to highlight the possible ways that CD133-mediated autophagy may affect the apoptosis of colorectal cancer cells. Targeting the aforementioned mechanisms may have a significant therapeutic role in eliminating CD133-positive stem cell-phenotype colorectal cancer cells, which can be responsible for tumor recurrence. [ABSTRACT FROM AUTHOR]

Patients with chronic myeloid leukemia (CML) respond to tyrosine kinase inhibitors (TKIs); however, CML leukemic stem cells (LSCs) exhibit BCR::ABL kinase-independent growth and are insensitive to TKIs, leading to disease relapse. To prevent this, new therapies targeting CML-LSCs are needed. Rates of mitochondria-mediated oxidative phosphorylation (OXPHOS) in CD34+CML cells within the primitive CML cell population are higher than those in normal undifferentiated hematopoietic cells; therefore, the inhibition of OXPHOS in CML-LSCs may be a potential cure for CML. NK-128 (C33H61NO5S) is a structurally simplified analog of JCI-20679, the design of which was based on annonaceous acetogenins. NK-128 exhibits antitumor activity against glioblastoma and human colon cancer cells by inhibiting OXPHOS and activating AMP-activated protein kinase (AMPK). Here, we demonstrate that NK-128 effectively suppresses the growth of CML cell lines and that the combination of imatinib and NK-128 is more potent than either alone in a CML xenograft mouse model. We also found that NK-128 inhibits colony formation by CD34+ CML cells isolated from the bone marrow of untreated CML patients. Taken together, these findings suggest that targeting OXPHOS is a beneficial approach to eliminating CML-LSCs, and may improve the treatment of CML. [ABSTRACT FROM AUTHOR]

This article discusses the concept of quiescence and dormancy in plants and their importance in plant development, acclimation, and survival. The article highlights recent research on the molecular and metabolic regulation of quiescence, as well as the ecological modeling and molecular perception of temperature in relation to dormancy. The integration of hormone and cell-to-cell signaling, as well as the role of epigenetic mechanisms in establishing and maintaining dormancy, is also explored. The article concludes by emphasizing the potential applications of this research in enhancing plant resilience in the face of climate change. [Extracted from the article]

The primary pathological hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, a critical midbrain region. In vitro models based on DA neurons provide a powerful platform for investigating the cellular and molecular mechanisms of PD and testing novel therapeutic strategies. A deep understanding of DA neuron development, including the signalling pathways and transcription factors involved, is essential for advancing PD research. This article first explores the differentiation and maturation processes of DA neurons in the midbrain, detailing the relevant signalling pathways. It then compares various in vitro models, including primary cells, immortalized cell lines, and stem cell‐based models, focusing on the advantages and limitations of each. Special attention is given to the role of immortalized and stem cell models in PD research. This review aims to guide researchers in selecting the most appropriate model for their specific research goals. Ethical considerations and clinical implications of using stem cells in PD research are also discussed. [ABSTRACT FROM AUTHOR]

The asymmetric cell division determines cell diversity and distinct sibling cell fates by mechanisms linked to mitosis. Many adult stem cells divide asymmetrically to balance self‐renewal and differentiation. The process of asymmetric cell division involves an axis of polarity and, second, the localization of cell fate determinants at the cell poles. Asymmetric division of stem cells is achieved by intrinsic and extrinsic fate determinants such as signaling molecules, epigenetics factors, molecules regulating gene expression, and polarized organelles. At least some stem cells perform asymmetric and symmetric cell divisions during development. Asymmetric division ensures that the number of stem cells remains constant throughout life. The asymmetric division of stem cells plays an important role in biological events such as embryogenesis, tissue regeneration and carcinogenesis. This review summarizes recent advances in the regulation of asymmetric stem cell division in model organisms. [ABSTRACT FROM AUTHOR]

OBJECTIVES Tracheal regeneration is challenging owing to its unique anatomy and low blood supply. Most tracheal regeneration applications require scaffolds. Herein, we developed bio-three-dimensional-printed scaffold-free artificial tracheas. METHODS We fabricated bio-three-dimensional-printed artificial tracheas. Their anterior surface comprised hyaline cartilage differentiated from mesenchymal stem cells, and their posterior surface comprised smooth muscle. Human bone marrow-derived mesenchymal stem cells were cultured and differentiated into chondrocytes using fibroblast growth factor-2 and transforming growth factor-beta-3. Initially, horseshoe-shaped spheroids were printed to cover the anterior surface of the artificial trachea, followed by the application of human bronchial smooth muscle cells for the posterior surface. After a 3-week maturing process, the artificial trachea was subjected to histological and immunohistochemical analyses. RESULTS The anterior surface of the artificial trachea comprised well-differentiated hyaline cartilage from human bone marrow-derived mesenchymal stem cells. Immunohistochemistry revealed that the smooth muscle expressed α-smooth muscle actin and smooth muscle myosin heavy chain 11. CONCLUSIONS A bio-three-dimensional-printed scaffold-free artificial trachea comprising different tissues at the front and back was successfully fabricated. [ABSTRACT FROM AUTHOR]

Endometriosis is a significant reproductive health issue with pain being the primaru symptom. The complex pain in endometriosis involves the activation of macrophages, inflammatory activators such as NF-kB, neural growth factors (NGF), cytokines, adhesive molecules (ICAM-1), and mediators (PGE2) which they are stimulate sensory nerve fibers and produce nociceptive signals. This study is aim for investigate the effect of Mesenchymal Stem Cell (MSC) administration on the expression of NF-kB, NGF, and PGE2 concentration in a mouse model of endometriosis. Thirty-three mices were randomly divided into 3 groups consist non-endometriosis (P0), endometriosis without treatment (P1), and endometriosis with MSC administration (P2). The results showed MSC administration significantly reduced the expression of NF-kB by found scoring 2 groups (P1: 6.96 ± 0.13 and P2: 4.446 ± 0.228) and NGF (P1: 7.118 ± 0.629 and P2: 4.927 ± 1.187) also PGE2 (P1:1005.862 ± 176.656 and P2: 891.218 ± 54.031. In onclusion, this study demonstrates that MSC administration can able reduce the expression of NF-kB and NGF, but not to PGE2. The suggestion we can said is the MSC have potential therapeutic value in managing endometriosis-asssosciated pain by modulating inflammatory and neurotrophic factors. [ABSTRACT FROM AUTHOR]

Differentiation approaches to obtain mesenchymal stem cells (MSCs) have gradually developed over the last few decades. The problem is that different protocols give different MSC types, making further research difficult. Here, we tried three different approaches to differentiate embryonic stem cells (ESCs) from early mesoderm to MSCs using serum-containing or xeno-free differentiation medium and observed differences in the cells' morphology, doubling rate, ability to form colonies, surface marker analysis, and multilineage differentiation potential of the obtained cell lines. We concluded that the xeno-free medium best fits the criteria of MSCs' morphology, growth kinetics, and surface marker characterization. In contrast, the serum-containing medium gives better potential for further MSC differentiation into osteogenic, chondrogenic, and adipogenic lineages. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the miRNA expression profile in Notch‐activated human dental stem pulp stem cells (DPSCs) and validated the functions of miRNAs in modulating the odonto/osteogenic properties of DPSCs. Methods: DPSCs were treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed, and miRNA expression was validated. Odonto/osteogenic differentiation was examined using alkaline phosphatase staining, Alizarin Red S staining, as well as odonto/osteogenic‐related gene and protein expression. Results: Fourteen miRNAs were differentially expressed in Jagged1‐treated DPSCs. Pathway analysis revealed that altered miRNAs were associated with TGF‐β, Hippo, ErbB signalling pathways, FoxO and Ras signalling. Target prediction analysis demonstrated that 7604 genes were predicted to be targets for these altered miRNAs. Enrichment analysis revealed relationships to various DNA bindings. Among differentially expressed miRNA, miR‐296‐3p and miR‐450b‐5p were upregulated under Jagged1‐treated conditions. Overexpression of miR‐296‐3p and miR‐450b‐5p enhanced mineralization and upregulation of odonto/osteogenic‐related genes, whereas inhibition of these miRNAs revealed opposing results. The miR‐296‐3p and miR‐450b‐5p inhibitors attenuated the effects of Jagged1‐induced mineralization in DPSCs. Conclusions: Jagged‐1 promotes mineralization in DPSCs that are partially regulated by miRNA. The novel understanding of these miRNAs could lead to innovative controlled mechanisms that can be applied to modulate biology‐targeted dental materials. [ABSTRACT FROM AUTHOR]

Life on Earth has been through numerous challenges over eons and, one way or another, has always triumphed. From mass extinctions to more daily plights to find food, unpredictability is everywhere. The adaptability of life-forms to ever-changing environments is the key that confers life's robustness. Adaptability has become synonymous with Darwinian evolution mediated by heritable genetic changes. The extreme gene-centric view, while being of central significance, at times has clouded our appreciation of the cell as a self-regulating entity informed of, and informing, the genetic data. An essential element that powers adaptability is the ability to regulate cell growth. In this review, we provide an extensive overview of growth regulation spanning species, tissues, and regulatory mechanisms. We aim to highlight the commonalities, as well as differences, of these phenomena and their molecular regulators. Finally, we curate open questions and areas for further exploration. [ABSTRACT FROM AUTHOR]

In developed economies, the growing number of older individuals is a pressing issue. As a result, research progress into ageing has emphasized the significance of staying healthy in one's later years. Stem cells have a fundamental role to play in fostering diverse cell types and necessary processes for tissue repair and regeneration. Stem cells experience the effects of ageing over time, which is caused by their functional deterioration. Changes to stem cells, their niches and signals from other tissues they interact with are crucial factors in the ageing of stem cells. Progress in single-cell RNA sequencing (scRNA-seq) technology has greatly advanced stem cell research. This review examines the mechanisms of stem cell ageing, its impact on health and investigates the potential of stem cell therapy, with a special emphasis on the skin. [ABSTRACT FROM AUTHOR]

Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-CreERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM). With the increasing prevalence of DM worldwide, the incidence of DKD remains high. If DKD is not well controlled, it can develop into chronic kidney disease or end-stage renal disease (ESRD), which places considerable economic pressure on society. Traditional therapies, including glycemic control, blood pressure control, blood lipid control, the use of renin–angiotensin system blockers and novel drugs, such as sodium–glucose cotransporter 2 inhibitors, mineralocorticoid receptor inhibitors and glucagon-like peptide-1 receptor agonists, have been used in DKD patients. Although the above treatment strategies can delay the progression of DKD, most DKD patients still ultimately progress to ESRD. Therefore, new and multimodal treatment methods need to be explored. In recent years, researchers have continuously developed new treatment methods and targets to delay the progression of DKD, including miRNA therapy, stem cell therapy, gene therapy, gut microbiota-targeted therapy and lifestyle intervention. These new molecular therapy methods constitute opportunities to better understand and treat DKD. In this review, we summarize the progress of molecular therapeutics for DKD, leading to new treatment strategies. [ABSTRACT FROM AUTHOR]

Background: There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a comprehensive and up-to-date meta-analysis is lacking. Before clinical translation, it is crucial to thoroughly understand the overall impact of stem cell-derived EVs on POF. Methods: PubMed, EMBASE, Cochrane Library, Web of Science were searched up to February 18, 2024. The risk of bias was evaluated according to Cochrane Handbook criteria, while quality of evidence was assessed using the SYRCLE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and sensitivity analysis and publication bias analysis were performed using Stata 14. Results: Data from 25 studies involving 339 animals were extracted and analyzed. The analysis revealed significant findings: stem cell-derived EVs increase ovary weight (SMD = 3.88; 95% CI: 2.50 ~ 5.25; P < 0.00001; I2 = 70%), pregnancy rate (RR = 3.88; 95% CI: 1.94 ~ 7.79; P = 0.0001; I2 = 0%), count of births (SMD = 2.17; 95% CI: 1.31 ~ 3.04; P < 0.00001; I2 = 69%) and counts of different types of follicles. In addition, it elevates the level of AMH (SMD = 4.15; 95% CI: 2.75 ~ 5.54; P < 0.00001; I2 = 88%) and E2 (SMD = 2.88; 95% CI: 2.02 ~ 3.73; P < 0.00001; I2 = 80%) expression, while reducing FSH expression (SMD = -5.05; 95% CI: -6.60 ~ -3.50; P < 0.00001; I2 = 90%). Subgroup analysis indicates that the source of EVs, animal species, modeling method, administration route, and test timepoint affected efficacy. Trial sequential analysis showed that there was sufficient evidence to confirm the effects of stem cell-derived EVs on birth counts, ovarian weights, and follicle counts. However, the impact of stem cell-derived EVs on pregnancy rates needs to be further demonstrated through more animal experimental evidence. Conclusions: Stem cell-derived EVs demonstrate safety and efficacy in treating POF animal models, with potential improvements in fertility outcomes. Trial registration: PROSPERO registration number: CRD42024509699. [ABSTRACT FROM AUTHOR]

BACKGROUND: Satellite cells are myogenic stem cells located between the muscle fiber membrane and the basement membrane. However, a comprehensive review of the aging mechanisms of satellite cells and their potential mitigation strategies is still lacking. This gap in knowledge hinders the effective guidance for current strategies aimed at attenuating skeletal muscle aging. OBJECTIVE: To review the mechanisms of satellite cell aging in skeletal muscle and the relevant strategies for mitigating this aging process. METHODS: Major databases were searched up to May 2023, including Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), WanFang Data, and VIP. Chinese and English search terms included “skeletal muscle, satellite cells, aging, mechanism, and solution strategy”. After strict inclusion and exclusion criteria were applied, 78 articles were finally included. RESULTS AND CONCLUSION: (1) Satellite cells, situated between the muscle fiber membrane and basement membrane, possess proliferative and differentiative potential. They usually remain in a quiescent state but become activated in response to muscle tissue stimuli, participating in processes of repair and restoration of normal tissue structure. Aging leads to a reduction in satellite cell numbers, resulting in symptoms such as muscle weakness and decreased endurance. (2) Mechanisms of satellite cell aging primarily involve diminished regenerative capacity, perturbed niche interactions with changing ecology, agedependent loss, and heterogeneity changes. Reduced satellite cell numbers and activity due to aging lead to slower muscle regeneration and increased injury recovery time. Errors during differentiation may occur, resulting in decreased muscle quality and function deterioration. (3) Strategies for mitigating satellite cell aging encompass modulation of the receptor environment of intra-body satellite cells, peripheral interventions to promote satellite cell regeneration, construction of human muscle models, and exercise and nutritional interventions to induce satellite cell proliferation. These strategies hold promise in offering novel insights and methods for satellite cell regeneration and treatment of skeletal muscle diseases. (4) Future research should delve into the mechanisms of satellite cell aging, explore the interaction between satellite cells and their niches, investigate the relationship of satellite cells with the immune system and mitochondrial function, and develop human muscle models to enhance research depth and accuracy. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is the standard of care for eligible patients with newly diagnosed multiple myeloma leading to prolonged progression free and overall survival. Successful engraftment following hematopoietic stem cell infusion requires adequate stem cell doses. Current mobilization regimens include granulocyte colony-stimulating factor (G-CSF) with or without plerixafor. Motixafortide is a recently approved agent that can be used in combination with G-CSF for mobilization. In the absence of any head-to-head trials comparing the two products, this article aims to outline the similarities and differences of these two agents. Though moxitafortide has a more favorable pharmacokinetic profile in comparison to plerixafor, in clinical trials, the agents demonstrated similar efficacy. In addition, the use of motixafortide in clinical practice may be limited by product cost as well as administration and monitoring requirements. [ABSTRACT FROM AUTHOR]

Various studies have been widely conducted on conditioned medium for the development of anti-aging preparations, including the utilization of stem cells, which present a promising alternative solution. This narrative review aims to understand the latest developments in various conditioned medium stem cell applications for anti-aging on the skin. A search of the Scopus database yielded publications of interest. The research focused on articles published without restrictions on the year. After finding 68 articles in the search results, they moved on to the checking phase. Upon comprehensive literature review, 23 articles met the inclusion criteria, while 45 articles were deemed ineligible for participation in this research. The results of the review indicate that conditioned medium from various stem cells has demonstrated success in reducing risk factors for skin aging, as proven in various tests. The successful reduction of the risk of skin aging has been established in vitro, in vivo, and in clinical trials. Given the numerous studies on the progress of exploring and utilizing conditioned medium, it is expected to provide a solution to the problem of skin aging. [ABSTRACT FROM AUTHOR]

With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise in promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological and behavioral deficits that frequently accompany ischemic stroke. These findings have led to a number of clinical trials that have thoroughly supported a strong safety profile for stem cell therapy in patients but have generated variable efficacy. As preclinical evidence continues to expand through the investigation of new cell lines and optimization of stem cell delivery, it remains critical for translational models to adhere to the protocols established through basic scientific research. With the recent shift in approach towards utilization of stem cells as a conjunctive therapy alongside standard thrombolytic treatments, key issues including timing, route of administration, and stem cell type must each be appropriately translated from the laboratory in order to resolve the question of stem cell efficacy for cerebral ischemia that ultimately will enhance therapeutics for stroke patients towards improving quality of life. [ABSTRACT FROM AUTHOR]

Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal disorders. The current literature reports that organic and artificial substances create bioscaffolds that imitate the inherent structure of the cornea, facilitating the attachment, growth, and specialization of stem cells. Sophisticated methods such as electrospinning, 3D bioprinting, and surface modification have been reported to enhance the characteristics of the scaffold. These bioscaffolds have been shown to greatly improve the survival of stem cells and facilitate the regrowth of corneal tissue in both laboratory and live animal experiments. In addition, the incorporation of growth factors and bioactive compounds within the scaffolds can promote a favorable milieu for corneal regeneration. To summarize, the advancement of these groundbreaking bioscaffolds presents a hopeful treatment strategy for the regeneration of the cornea, which has the potential to enhance the results for individuals suffering from corneal disorders. This study highlights the possibility of utilizing the fields of biomaterials science and stem cell treatment to tackle medical demands that have not yet been satisfied in the field of ophthalmology. [ABSTRACT FROM AUTHOR]

miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE‐secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV‐secreting cell and understanding the biological cargo of EVs to develop EV‐based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); early‐stage hESC‐RPE (20–21 days in culture), mid‐stage hESC‐RPE (30–31 days in culture) and late‐stage hESC‐RPE (60–61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV‐based intraocular therapeutics utilizing RPE‐secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases. [ABSTRACT FROM AUTHOR]

Introduction: According to the World Health Organization (WHO), by 2050 at least 700 million people will need access to hearing care and hearing rehabilitation services. The search for cell or gene therapies has been intensifying, and stem cell therapy looks a promising candidate to support hearing regeneration and reduce these numbers. The aim of this study is to provide an overview of current advances in stem cell-based therapies for cochlear hair cell regeneration and the processes being developed for future applicability. Material and methods: Identification and review of all articles in the databases PubMed, Web of Science, and PLoS One using the terms stem cell, auditory hair cell regeneration, and mammalian during February 2023 and following the PRISMA guidelines. Results: 50 articles were obtained, published between 2003 and 2022 and were systematically analyzed. The current research quantity is limited and further studies are needed, particularly in human tissue. Conclusion: The simultaneous use of cell therapy and gene therapy may lead to more promising results. Moreover, advances in cochlear hair cell regeneration with stem cells suggest there is a realistic potential to make the technique a useful future therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cleft lip alone or a combination of cleft lip and palate (CLP) is a common developmental abnormality in the craniofacial region. This umbrella review aims to identify promising avenues for treatment using stem cell therapy. Materials and Methods: Systematic reviews from 2014 to 2024 were searched among databases like PubMed, Medline, and Google Scholar. PRISMA guidelines were employed to ensure the thoroughness of the search. A quality assessment (ROBIS) of the included reviews was conducted to ensure the reliability and validity of the synthesized evidence. Results: Five systematic reviews were selected for this umbrella review. Results show that stem cell therapy, specifically using mesenchymal stem cells (MSCs) and adipocyte stem cells (ADSCs), promotes bone regeneration in CLP deformities. Although multiple studies have established the effectiveness of diverse types of stem cells in treating CLP, important considerations including safety concerns, methodological variability, and the need for standardization have been identified. The fact that the number of relevant systematic reviews that matched our inclusion criteria was limited could affect this research's robustness and may limit the breadth and depth of evidence synthesis. Definitive conclusions could not be reached due to variation among treatments and outcomes. Conclusions: The examined studies highlight the potential of stem cell therapy as a complementary approach to existing treatments for CLP. However, there are challenges that need to be addressed, including concerns regarding safety, variations in methodologies, and the need for standardization. Exploring the potential of other stem cell types may further enhance treatment outcomes for CLP patients. [ABSTRACT FROM AUTHOR]

A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20–25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells. [ABSTRACT FROM AUTHOR]

BACKGROUND Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. OBJECTIVE AND RATIONALE This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. SEARCH METHODS A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine). OUTCOMES The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors. WIDER IMPLICATIONS Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field. REGISTRATION NUMBER Not applicable. [ABSTRACT FROM AUTHOR]

Clinical relevance: Findings from this study examining Australian optometrists' insights into ocular stem cell (SC) therapies have capacity to inform continuing professional development (CPD) about these interventions. Background: This study investigated Australian optometrists' knowledge, views, experiences, and preferred education sources regarding ocular SC therapies. Methods: An online survey was distributed to optometrists via Optometry Australia, Mivision magazine, professional groups, and social media from August 2020 to March 2021. Data were collected on demographics, and SC knowledge, awareness and experience. Results: Of 81 optometrists who completed the survey, many were metropolitan-based (85%), worked in independent practice (47%), female (56%) and >46 years of age (45%). Approximately one-fifth indicated awareness of ocular SC therapies used in standard practice; one-third had knowledge of SC clinical trials. The most noted SC therapies were for corneal disease in the United States [US] (72%) and Australia (44%). Respondents identified the availability of SC therapies for dry eye disease in Australia and the US (39% and 44% respectively), despite no regulatory-approved treatments for this indication. Clinical trials investigating inherited retinal and corneal diseases in Australia were the most commonly identified (44% and 36%, respectively). Half the respondents felt 'unsure' about the quality of evidence for treating eye conditions using SCs. One-fifth indicated concerns with these therapies; of these, most mentioned efficacy (82%), safety (76%) and/or cost (71%). About one-fifth reported being asked for advice about SCs by patients. Two-thirds felt neutral, uncomfortable, or very uncomfortable providing this advice, due to lack of knowledge or the topic being beyond their expertise. Over half (57%) were unsure if clinical management should change if patients received SC therapies. Respondents were receptive to face-to-face education. Conclusion: Some optometrists responding to this survey were aware of ocular SC therapies and/or clinical trials. CPD programs may assist with maintaining currency in this evolving field. [ABSTRACT FROM AUTHOR]

The formation of stomata presents a compelling model system for comprehending the initiation, proliferation, commitment and differentiation of de novo lineage‐specific stem cells. Precise, timely and robust cell fate and identity decisions are crucial for the proper progression and differentiation of functional stomata. Deviations from this precise specification result in developmental abnormalities and nonfunctional stomata. However, the molecular underpinnings of timely cell fate commitment have just begun to be unravelled. In this review, we explore the key regulatory strategies governing cell fate commitment, emphasizing the distinctions between embryonic and postembryonic stomatal development. Furthermore, the interplay of transcription factors and cell cycle machineries is pivotal in specifying the transition into differentiation. We aim to synthesize recent studies utilizing single‐cell as well as cell‐type‐specific transcriptomics, epigenomics and chromatin accessibility profiling to shed light on how master‐regulatory transcription factors and epigenetic machineries mutually influence each other to drive fate commitment and maintenance. Summary statement: In this review, we delve into the molecular mechanisms underlying timely and precise cell fate commitment during stomatal development. Emphasis is made on the differences between embryonic and postembryonic stomatal differentiation. We highlight recent discoveries on the transcriptional circuits that initiate and fortify stomatal fate transitions, as well as the epigenetic processes that facilitate fate commitment and maintenance. [ABSTRACT FROM AUTHOR]

This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue‐engineered allograft (Eng‐allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re‐ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng‐allograft, which had been revitalized with autologous bone marrow‐derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd‐SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng‐allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng‐allograft group was significantly lower than that of the autograft group with higher graft rupture at the host−graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd‐SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Magnetic nanomaterials have biological activities such as promoting osteogenic differentiation of stem cells and inhibiting osteoclast formation, and can effectively promote the healing of injured bone tissue under the synergistic effect of magnetic fields. They have a very broad application prospect in bone injury repair. OBJECTIVE: To review the mechanism of magnetic nanomaterials and magnetic fields promoting bone repair, as well as their research progress in the field of bone injury repair. METHODS: Relevant literature search was conducted in PubMed and Web of Science databases with the search terms "magnetic nanomaterials, magnetic field, bone repair, bone tissue engineering, stem cell, osteoblast, osteoclast." The time limit of literature search was from 2003 to 2023, which was screened and analyzed. Some classic articles were manually retrieved, and 98 articles were finally included for RESULTS AND CONCLUSION: (1) Magnetic nanomaterials have biological effects such as promoting osteoblast differentiation, inhibiting osteoclast formation and regulating the immune microenvironment. In addition, magnetic nanomaterials can regulate the physicochemical properties of tissue engineering scaffolds, such as mechanical properties and surface morphology, and endowed with magnetic properties, which is conducive to the regulation of the adhesion, proliferation and osteogenic differentiation of stem cells. (2) The magnetic field has the ability to regulate multiple cell signaling pathways to promote osteoblast differentiation, inhibit osteoclast formation, stimulate angiogenesis and other biological effects, thus accelerating the healing of damaged bone tissue. (3) The joint application of magnetic nanomaterials and magnetic field accelerates the repair of bone damage by activating mechanotransduction, increasing the content of intracellular magnetic nanoparticles, and enhancing the effect of micro-magnetic field, which provides a new idea for the research of bone tissue engineering. (4) Magnetic field has demonstrated definite efficacy in the treatment of clinical fractures, osteoporosis, and osteoarthritis diseases, which is beneficial for bone tissue growth, reducing bone loss, alleviating pain, and improving the quality of life of patients. (5) Magnetic nanomaterials and magnetic fields have great potential for application in bone damage repair and regeneration, but the interaction mechanism between magnetic nanomaterials, magnetic fields, and cells has not been fully elucidated. Moreover, the key parameters of magnetic fields that regulate intracellular molecular events, including the type, intensity, frequency, duration, and mode of the magnetic field, as well as the precise biological effects of a specific magnetic field on osteoblasts and the underlying mechanisms, have yet to be defined. (6) Further attention needs to be paid to the effects on osteoclasts, nerves, blood vessels, and immune cells in the microenvironment of damaged tissues. Finally, the safety of magnetic materials for human use is yet to be systematically studied in terms of their distribution, metabolism, and acute and chronic toxicities. [ABSTRACT FROM AUTHOR]

BACKGROUND: 3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function, making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE: To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to, as well as their regulatory status and challenges. METHODS: With “organoid, stem cell, disease model, 3D printing technology, medical field” as Chinese and English search terms, we searched PubMed, Elsevier, WanFang, and CNKI databases to summarize and analyze organoid products at home and abroad, summarize the application of organoid technology in the medical field, and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION: Organoids can break the limitations of traditional cell and animal models, avoid the ethical problems existing in clinical research, and have a high similarity to the source organ, a more similar performance to the physiology and pathology of human systems, and genetic stability, which has great advantages in current research. Organoids have been applied in the following fields: efficacy evaluation studies (preclinical models), including intestinal organoids, kidney organoids, liver organoids, gallbladder organoids, lung organoids, brain organoids, heart organoids, skin organoids, and reproductive system organoids; research on infectious diseases; cancer research and precision therapy; regenerative medicine; immune organoids. Although the United States, the European Union and China do not have perfect regulatory provisions, they are trying to promote the formulation of organoid regulatory laws and regulations. In China, although no organoid medical device products have been listed for the time being, its related regenerative medicine products have made breakthroughs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The small-diameter blood vessel prosthesis faces the problem of lumen stenosis or even occlusion due to thrombogenesis and intimal hyperplasia after transplantation. The application of stem cells as seed cells to achieve endothelialization of blood vessel prosthesis helps to improve the long-term patency rate after vascular graft transplantation. OBJECTIVE: To summarize the research progress of the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis. METHODS: The relevant articles published on PubMed and WanFang databases from 2013 to 2023 were retrieved by the first author. Chinese and English search terms included “vascular graft, tissue-engineered blood vessel/vascular tissue engineering, endothelialization, stem cells, endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, embryonic stem cells.” The relative articles in the domestic and overseas about the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis in the past 10 years were retrieved. A total of 552 articles were initially found and we finally selected 81 articles to review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) The low long-term patency rate restricts the application of small-diameter blood vessel prosthesis in clinic. The main causes of low long-term patency rate are thrombogenesis and intimal hyperplasia. The endothelium of native vessels has the function of anti-thrombogenesis and intimal hyperplasia. Endothelialization can simulate the function of native vessels, which is an effective way to improve long-term patency rate. (2) The small-diameter blood vessel prosthesis will undergo in vivo endothelialization after being implanted, but it is difficult to form complete endothelium. Stem cells have the potential to differentiate into endothelial cells. Recruiting stem cells in vivo or seeding them on the inner surface of blood vessel prosthesis in vitro is research strategy to achieve endothelialization. (3) The long-term patency rate of small-diameter blood vessel prosthesis has been improved to a certain extent through seeding endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells. Each has its own advantages. Endothelial progenitor cells are easy to obtain and can be directly used for seeding. Mesenchymal stem cells come from a wide range of sources and have the function of paracrine and immunological regulation. Induced pluripotent stem cells are rich in sources and the immunogenicity can be eliminated. Embryonic stem cells have a strong proliferative ability and can differentiate into many cells. (4) The application of stem cells in blood vessel prosthesis has not yet been transformed into clinic. Further researches are needed to promote clinical translation. [ABSTRACT FROM AUTHOR]

AbstractGraphene oxide (GO) is widely used in bone tissue engineering due to its good biocompatibility and proliferation, and is often used in combination with other hydrogels, which not only reduces the cytotoxicity of GO but also improves the mechanical properties of the hydrogels. We developed injectable carboxymethyl chitosan (CMC)/hydroxyethyl cellulose (HEC)/β-tricalcium phosphate (β-TCP)/GO hydrogel via hydrogen bonding cross-linked between (CMC) and (HEC), also, calcium cross-linked by β-TCP was also involved to further improvement of mechanical properties of the hydrogel, and incorporate different concentration of GO in these hydrogel systems. The characterization of the novel hydrogel was tested by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The swelling ratio and mechanical properties were investigated, the results showed that the addition of GO was able to reduce the swelling rate of hydrogels and improve their mechanical properties, with the best effect in the case of 1 mg/mL content. In vivo experimental studies showed that the hydrogel significantly promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), with the best effect at a concentration of 2 mg/mL. The results of the cellular experiments were similar. Therefore, the novel environment-friendly and non-toxic injectable CMC/HEC/β-TCP/GO hydrogel system may have potential applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their therapeutic advantages are manifested in the management of a broad spectrum of diseases, and their dosing versatility are exemplified by systemic administration and local delivery. Furthermore, the activation and regulation of various signaling cascades have provided foundation for the claimed curative effects of exosomal therapy. Unlike other relevant reviews focusing on the upstream aspects (e.g., yield, isolation, modification), and downstream aspects (e.g. phenotypic changes, tissue response, cellular behavior) of stem cell-derived exosome therapy, this unique review endeavors to focus on various affected signaling pathways. After meticulous dissection of relevant literature from the past five years, we present this comprehensive, up-to-date, disease-specific, and pathway-oriented review. Exosomes sourced from various types of stem cells can regulate major signaling pathways (e.g., the PTEN/PI3K/Akt/mTOR, NF-κB, TGF-β, HIF-1α, Wnt, MAPK, JAK-STAT, Hippo, and Notch signaling cascades) and minor pathways during the treatment of numerous diseases encountered in orthopedic surgery, neurosurgery, cardiothoracic surgery, plastic surgery, general surgery, and other specialties. We provide a novel perspective in future exosome research through bridging the gap between signaling pathways and surgical indications when designing further preclinical studies and clinical trials. [ABSTRACT FROM AUTHOR]

The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. Methods: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. Results: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. Conclusions: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration. [ABSTRACT FROM AUTHOR]