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This study aimed to explore the therapeutic potential of human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) in the emerging approach of bridge to recovery for severe heart failure with ventricular assist devices. We used a rat model of heterotopic heart transplantation (HTx) to mimic ventricular assist device support and heart unloading. HiCTs were created by inserting gelatin hydrogel microspheres between cell sheets made from hiPSC-derived cardiovascular cells. Male athymic nude rats underwent myocardial infarction (MI) and were divided into the following groups: MI (loaded, untreated control), MI + HTx (unloaded, untreated control), MI + HTx + HiCT (unloaded, treated), and MI + HiCT (loaded, treated). HiCTs were placed on the epicardium of the heart in treated groups. We evaluated HiCT engraftment, fibrosis, and neovascularization using histologic analysis. After 4 weeks, HiCTs successfully engrafted in 5 of 6 rats in the MI + HTx + HiCT group (83.3%). The engrafted HiCT area was greater under unloaded conditions (MI + HTx + HiCT) than loaded conditions (MI + HiCT) (P <.05). MI + HTx + HiCT had a significantly smaller infarct area compared with MI and MI + HTx. The MI + HTx + MiCT group exhibited greater vascular density in the border zone than MI and MI + HTx. HiCT treatment suppressed cardiomyocyte atrophy due to left ventricular unloading (P =.001). The protein level of muscle-specific RING finger 1, an atrophy-related ubiquitin ligase, was lower in the MI + HTx + HiCT group than in MI + HTx (P =.036). Transplanting HiCTs into ischemic hearts under unloaded conditions promoted engraftment, neovascularization, attenuated infarct remodeling, and suppressed myocyte atrophy. These results suggest that HiCT treatment could contribute to future advancements in bridge to recovery. [ABSTRACT FROM AUTHOR]

[Display omitted] • The contribution of autophagy on stem cell function and oral tissue regeneration. • Molecular mechanisms involved in autophagy during oral tissue regeneration. • The diverse roles of autophagy in different oral tissues. • Possible autophagy regulation methods to enhance oral tissue regeneration. Oral health is of fundamental importance to maintain systemic health in humans. Stem cell-based oral tissue regeneration is a promising strategy to achieve the recovery of impaired oral tissue. As a highly conserved process of lysosomal degradation, autophagy induction regulates stem cell function physiologically and pathologically. Autophagy activation can serve as a cytoprotective mechanism in stressful environments, while insufficient or over-activation may also lead to cell function dysregulation and cell death. This review focuses on the effects of autophagy on stem cell function and oral tissue regeneration, with particular emphasis on diverse roles of autophagy in different oral tissues, including periodontal tissue, bone tissue, dentin pulp tissue, oral mucosa, salivary gland, maxillofacial muscle, temporomandibular joint, etc. Additionally, this review introduces the molecular mechanisms involved in autophagy during the regeneration of different parts of oral tissue, and how autophagy can be regulated by small molecule drugs, biomaterials, exosomes/RNAs or other specific treatments. Finally, this review discusses new perspectives for autophagy manipulation and oral tissue regeneration. Overall, this review emphasizes the contribution of autophagy to oral tissue regeneration and highlights the possible approaches for regulating autophagy to promote the regeneration of human oral tissue. [ABSTRACT FROM AUTHOR]

[Display omitted] Inborn errors of immunity (IEI) often lack specific disease models and personalized management. Signal transducer and activator of transcription (STAT)-1 gain of function (GoF) is such example of an IEI with diverse clinical phenotype with unclear pathomechanisms and unpredictable response to therapy. Limitations in obtaining fresh samples for functional testing and research further highlights the need for patient-specific ex vivo platforms. Using STAT1-GoF as an example IEI, we investigated the potential of patient-derived expanded potential stem cells (EPSC) as an ex vivo platform for disease modeling and personalized treatment. We generated EPSC derived from individual STAT1-GoF patients. STAT1 mutations were confirmed with Sanger sequencing. Functional testing including STAT1 phosphorylation/dephosphorylation and gene expression with or without Janus activating kinase inhibitors were performed. Functional tests were repeated on EPSC lines with GoF mutations repaired by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) editing. EPSC were successfully reprogrammed from STAT1-GoF patients and expressed the same pluripotent makers as controls, with distinct morphologic differences. Patient-derived EPSC recapitulated the functional abnormalities of index STAT1-GoF patients with STAT1 hyperphosphorylation and increased expression of STAT1 and its downstream genes (IRF1, APOL6, and OAS1) after IFN-γ stimulation. Addition of ruxolitinib and baricitinib inhibited STAT1 hyperactivation in STAT1-GoF EPSC in a dose-dependent manner, which was not observed with tofacitinib. Corrected STAT1 phosphorylation and downstream gene expression were observed among repaired STAT1-GoF EPSC cell lines. This proof-of-concept study demonstrates the potential of our patient-derived EPSC platform to model STAT1-GoF. We propose this platform when researching, recapitulating, and repairing other IEI in the future. [ABSTRACT FROM AUTHOR]

Cell-based therapy has emerged as a promising avenue for post-stroke recovery. A significant challenge lies in tracking the distribution and engraftment of transplanted cells within the target cerebral tissue. To address this, we turn to the potential of Brain MRI detection of mesenchymal stem cells (MSCs), achieved by labeling these cells with superparamagnetic iron oxide (SPIO). This is the first report of a technique to label canine MSCs using a commercially available SPIO, Molday ION Rhodamine B (MIRB), to optimize both viability and labeling efficacy for transplantation purposes." Canine MSCs were incubated with addition of different MIRB concentration from 0, 10, 20, 30 μg Fe/ml. The cellular uptake of MIRB was confirmed through the analysis of fluorescent images and flow cytometry. The morphological characteristics of MSCs were assessed via microscopic visualization. Cellular viability was evaluated using both a cellometer and flow cytometry. Fluorescent microscopic images of all MIRB incubated MSCs groups show >70% labeled cells with homogenous signal intensity. Notably, the morphology of MSCs remained unaltered in the 10 μg Fe/ml group compared to the control group. Furthermore, among the labeled groups, the 10 μg Fe/ml concentration exhibited the highest viability when assessed using two different flow cytometry methods (95.3%, p < 0.05). This study successfully labels canine MSCs with MIRB. The optimal concentration of 10 μg Fe/ml demonstrates optimal viability, labeling efficacy, and preserved cellular morphology. [ABSTRACT FROM AUTHOR]

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive glass filler capable of releasing various ions. A culture medium to which was added an S-PRG filler eluate rich in boron was reported to enhance alkaline phosphatase (ALP) activity in human dental pulp-derived stem cells (hDPSC). To clarify the role of boron eluted from S-PRG fillers, the modified S-PRG filler eluate with different boron concentrations was prepared by using an anion exchange material. Therefore, elemental mapping analysis of anion exchange material, adsorption ratio, hDPSCs proliferation and ALP activity were evaluated. For statistical analysis, Kruskal-Wallis test was used, with statistical significance determined at p<0.05. ALP activity enhancement was not observed in hDPSC cultured in the medium that contained the S-PRG filler eluate from which boron had been removed. The result suggested the possibility that an S-PRG filler eluate with controlled boron release could be useful for the development of novel dental materials. [ABSTRACT FROM AUTHOR]

This study aims to investigate the ability of umbilical cord mesenchymal stem cells (UC-MSC) to enhance the regeneration of pulp-dentin complex in immature permanent teeth with irreversible pulpitis. A total of 32 mandibular premolar teeth with immature apices in 5 dogs were used in this in-vivo randomized controlled trial (RCT). Eight healthy teeth without pre-existing pathosis served as the positive control samples and received no treatment, while in another 8 teeth, the pulp was completely extirpated (negative control). Class V cavities were prepared to induce inflammation in the remaining 16 teeth (groups 3 and 4) and the pulp was extirpated 2-4 mm short of the radiographic apex. Of the 16, the 8 teeth in group 4 received 1 mL of cord blood stem cells with a hydrogel scaffold. Blood clots were covered with mineral trioxide aggregates at the cementoenamel junction in the experimental groups, and teeth were filled with RMGI and composite. Three months later, block sections were removed for histologic evaluations for the evaluation of postoperative apical closure, degree of inflammation, and presence of normal pulp tissue. The data were statistically analyzed with the chi-square test (P <.05). All teeth with complete pulp extirpation demonstrated pulpal necrosis with no postoperative closure of their apices, while apical closure was seen in all the teeth in the remaining groups. There was a statistically significant (P <.001) difference in the presence of inflammation and normal pulp tissue between the experimental groups. The teeth in group 3 showed normal pulp tissue extending to the level of MTA, but there was inflammation within the canal space. In contrast, the teeth in the UC-MSC group demonstrated organized, normal pulp tissue with no inflammation. Based on these results, the regeneration of the pulp-dentin complex is possible with no inflammation when UC-MSCs are used and 2-4 mm of the apical pulp remains intact in immature teeth with irreversible pulpitis. [ABSTRACT FROM AUTHOR]

The regeneration of pulp tissue is crucial for true regenerative endodontic treatment, which requires a reduction in osteogenic differentiation. Garcinol, a histone acetyltransferase inhibitor, is a natural regulator that is known to suppress the osteogenic differentiation of dental pulp stem cells. In this study, the inhibitory effect of garcinol on the osteogenic differentiation of human dental pulp stem cells (hDPSCs) was evaluated using three-dimensional culture under in vitro and in vivo conditions. hDPSCs were obtained from caries-free third molars and cultured with 10 μM garcinol for 7 days in an ultra-low attachment plate. The cell stemness and expression of osteogenic differentiation-related genes were analyzed using reverse transcription-polymerase chain reaction and single-cell analysis. A transplantation experiment was performed in mice to investigate whether garcinol-treated hDPSCs showed restrained osteogenic differentiation. hDPSCs cultured in the U-shaped ultra-low attachment plate showed the highest expression of stemness-related genes. Garcinol-treated hDPSCs demonstrated downregulation of osteogenic differentiation, with lower expression of bone sialoprotein, which is related to bone formation, and higher expression of dentin sialophosphoprotein, which is related to dentin formation. However, the garcinol-treated hDPSCs did not show any alterations in their stemness. Consistent results were observed in the transplantation experiment in mice. Garcinol reduced the osteogenic differentiation of hDPSCs, which can contribute to true regenerative endodontic treatment. [ABSTRACT FROM AUTHOR]

Cancers of the alimentary tract, including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, are common comorbidities of obesity. Prolonged, excessive delivery of macronutrients to the cells lining the gut can increase one's risk for these cancers by inducing imbalances in the rate of intestinal stem cell proliferation vs differentiation, which can produce polyps and other aberrant growths. We investigated whether ceramides, which are sphingolipids that serve as a signal of nutritional excess, alter stem cell behaviors to influence cancer risk. We profiled sphingolipids and sphingolipid-synthesizing enzymes in human adenomas and tumors. Thereafter, we manipulated expression of sphingolipid-producing enzymes, including serine palmitoyltransferase (SPT), in intestinal progenitors of mice, cultured organoids, and Drosophila to discern whether sphingolipids altered stem cell proliferation and metabolism. SPT, which diverts dietary fatty acids and amino acids into the biosynthetic pathway that produces ceramides and other sphingolipids, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the sphingolipid biosynthesis pathway are up-regulated in human intestinal adenomas. They produce ceramides, which serve as prostemness signals that stimulate peroxisome-proliferator activated receptor-α and induce fatty acid binding protein-1. These actions lead to increased lipid utilization and enhanced proliferation of intestinal progenitors. Ceramides serve as critical links between dietary macronutrients, epithelial regeneration, and cancer risk. These studies demonstrate that ceramides, which are products of fat and protein metabolism, may link unhealthy diets to the formation of intestinal polyps that seed cancer. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a prevalent inflammatory skin disorder characterized by skin barrier dysfunction, thymic stromal lymphopoietin (TSLP) production and an imbalance in the Th1/Th2 immune response. While numerous studies have examined the therapeutic potential of adipose-derived stem cells (ADSC) in repairing and regenerating damaged skin tissues caused by AD, the effects of membrane-free stem cell components derived from ADSC extract (ADSCE) on AD have not been investigated. Objectives: The objective of this study was to investigate the alleviating effects of ADSCE on AD in mice and validate the therapeutic application of ADSCE on AD. Methods: An AD-like lesion was induced by the administration of 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin of NC/Nga mice. Then, ADSCE was administered subcutaneously for 3 weeks. Dermatitis score, epidermal thickness, transepidermal water loss (TEWL), and serum levels of immunoglobulin E (IgE) were measured. Expression of the skin barrier proteins and inflammatory cytokines were measured by western blotting and quantitative real-time polymerase chain reaction. Results: The administration of ADSCE demonstrated a significant amelioration in several skin diseases, as indicated by improvements in dermatitis score, epidermal thickness, TEWL, and total blood levels of IgE. ADSCE treatment led to an upregulation in the expression of various skin barrier proteins, including involucrin, loricrin, occludin, and zonula occludens-1. In addition, ADSCE inhibited the infiltration of mast cells and the expression of TSLP. Expression of inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 β, IL-4, and inducible nitric oxide synthase, was also lowered by ADSCE. Conclusions: The use of ADSCE resulted in enhanced skin features and exerted anti-inflammatory properties on AD-like lesions in mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (=2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group. METHODS: The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricularvascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and x3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16). RESULTS: The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall P=0.007) compared with controls, whereas ventricular-vascular coupling was higher in both survivor groups as was arterial elastance in long-term SCT survivors (ie, worse; P<0.01 for all). CONCLUSION: This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors. [ABSTRACT FROM AUTHOR]

Feline chronic gingivostomatitis (FCGS) is a painful, immune-mediated, oral mucosal inflammatory disease in cats. The etiology of FCGS remains unclear, with evidence pointing potentially toward a viral cause. Full-mouth tooth extraction is the current standard of care, and cats that are non-responsive to extraction therapy may need lifelong medical management and, in some cases, euthanasia. Adipose-derived mesenchymal stromal cells (adMSCs) have been demonstrated to have advantages in the treatment and potentially the cure of non-responsive FCGS in cats. Therefore, adMSCs have attracted a series of ongoing clinical trials in the past decade. AdMSC therapy immediately after full-mouth tooth extraction was not explored, and we postulate that it may benefit the overall success rate of FCGS therapy. Here, we aim to summarize the current knowledge and impact of adMSCs for the therapeutic management of FCGS and to suggest a novel modified approach to further increase the efficacy of FCGS treatment in cats. [ABSTRACT FROM AUTHOR]

Although there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental pulp regeneration is an innovative procedure for reviving dental pulp, if feasible for the entire tooth. Upon tooth injury, activated platelets release serotonin and dopamine in bulk to mobilize dental pulp stem cells to mediate natural dental repair. This has induced research on the role of neurotransmitters in increasing the proliferation rate of stem cells. This review also covers prospective future treatments for dental pulp regeneration. A literature search was performed via PubMed and ScienceDirect from 2001 to 2022, using the keywords "neurotransmitter," "stem cell," "tooth regeneration," "tooth repair," "regenerative dentistry," and "dental pulp." Different inclusion/exclusion criteria were used, and the search was restricted to English articles. Nine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected. Neurotransmitters were found to interact with dental stem cells. Evidence pointing to neurotransmitters as a factor in the increased proliferation of stem cells was found. This review thus gives hope for tooth pulp regeneration and repair. [ABSTRACT FROM AUTHOR]

Neuroblastoma arises from aberrancies in neural stem cell differentiation. PIM kinases contribute to cancer formation, but their precise role in neuroblastoma tumorigenesis is poorly understood. In the current study, we evaluated the effects of PIM kinase inhibition on neuroblastoma differentiation. Versteeg database query assessed the correlation between PIM gene expression and the expression of neuronal stemness markers and relapse free survival. PIM kinases were inhibited with AZD1208. Viability, proliferation, motility were measured in established neuroblastoma cells lines and high-risk neuroblastoma patient-derived xenografts (PDXs). qPCR and flow cytometry detected changes in neuronal stemness marker expression after AZD1208 treatment. Database query showed increased levels of PIM1, PIM2, or PIM3 gene expression were associated with higher risk of recurrent or progressive neuroblastoma. Increased levels of PIM1 were associated with lower relapse free survival rates. Higher levels of PIM1 correlated with lower levels of neuronal stemness markers OCT4, NANOG, and SOX2. Treatment with AZD1208 resulted in increased expression of neuronal stemness markers. Inhibition of PIM kinases differentiated neuroblastoma cancer cells toward a neuronal phenotype. Differentiation is a key component of preventing neuroblastoma relapse or recurrence and PIM kinase inhibition provides a potential new therapeutic strategy for this disease. • PIM kinases are oncogenes implicated in numerous malignancies. • Knowledge about the role of PIM kinases in neuroblastoma is lacking. • Differentiation is a key component of neuroblastoma therapy to prevent relapse or recurrence. • PIM kinases serve as a novel potential therapeutic target to promote neuroblastoma differentiation. [ABSTRACT FROM AUTHOR]

Salivary gland function impairment is one example of a Type 2 Diabetes Mellitus (T2DM) consequence caused by a loss of microcirculation. Mesenchymal stem cells' (MSCs) metabolite may modulate the immune response and fight pathogen infection through the synthesis of cathelicidin (LL-37) for tissue regeneration. Objectives to investigate the active compound of the MSCs' metabolite, namely cathelicidin (LL-37), which binds to the effects of interleukin (IL)-10, IL-17, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), tumor growth factor beta (TGFß), insulin growth factor (IGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), tissue inhibitor matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase (MMP)- 8 and -9, dectin, flaggelin, and peptidoglycan through a bioinformatics approach, in silico study. RCSB PDB was used to prepare the peptide Cathelicidin (LL37) (RCSB ID: 2K6O) and the biomarker targets for IL-10, VEGF, FGF2, IGF, HGF, EGF, TGFß, PDGF, TIMP-1, Dectin, Flagelin, Peptidoglycan, IL-17, MMP-9, and MMP-8. PyMol v2.5 software for molecular docking optimization and standard publication-style visualization was used to remove water molecules and ligand impurities from target surfaces. Cathelicidin (LL-37) has a great negative binding energy value with IL-10, VEGF, FGF2, IGF, HGF, EGF, TGFß, PDGF, TIMP1, Dectin, Flagelin, Peptidoglycan, IL-17, MMP-9, and MMP-8. Cathelicidins (LL-37) in MSC's metabolite has high negative binding energy value that may inhibits pro-inflammatory cytokines, microbial, tissue degradation enzyme related biomarkers and increase anti-inflammatory cytokines and growth factor as documented in silico. [ABSTRACT FROM AUTHOR]

Decellularized extracellular matrix (dECM) is a valuable tool for generating three-dimensional in vitro tumor models that effectively recapitulate tumor-extracellular matrix (ECM) interactions. However, in current culture models, the components and structures of dECM are enzymatically disrupted to form hydrogels, making it difficult to recapitulate the native ECM. Additionally, when studying ECM-cell interactions, large-volume tumor culture models are incompatible with traditional experimental techniques and the nutrient-oxygen concentration gradient, which is a significant confounding factor. To address these issues, we developed a decellularized brain extracellular matrix slice (dBECMS) glioblastoma (GBM) culture model. This model possesses good light transmittance and substance diffusivity, making it compatible with traditional experimental techniques without forming nutrient-oxygen concentration gradients. Through transcriptomic analysis, we found that native brain ECM has a broad impact on glioma cells; the impact involves the ECM-ECM receptor interactions and the ECM and metabolic reprogramming. Further experiments demonstrated that dBECMS promoted glucose consumption and lactate production in GBM cells. Silver staining experiments revealed abundant proteins in the media of dBECMS, suggesting the degradation of the brain ECM by GBM cells. Transcriptome analysis also showed that the dBECMS-GBM culture model more accurately recapitulated the transcriptional profile of GBM than the two-dimensional culture. We experimentally demonstrated that the dBECMS-GBM model enhanced the resistance of GBM cells to temozolomide and increased the stemness of GBM cells. Additionally, we demonstrated the feasibility of the dBECMS-GBM model as a platform for drug response modeling. The decellularized brain extracellular matrix (ECM) slice glioblastoma culture model mimics the interaction between native brain ECM and glioblastoma when glioblastoma infiltrates the brain and reveals the effects of native brain ECM on glioblastoma metabolism, ECM reprogramming, drug responsiveness, and stemness. [Display omitted] [ABSTRACT FROM AUTHOR]

Enteroids are miniature self-organising three-dimensional (3D) tissue cultures which replicate much of the complexity of the intestinal epithelium. We recently developed an apical-out leukocyte-containing chicken enteroid model providing a novel physiologically relevant in vitro tool to explore host–pathogen interactions in the avian gut. However, the replicate consistency and culture stability have not yet been fully explored at the transcript level. In addition, causes for the inability to passage apical-out enteroids were not determined. Here we report the transcriptional profiling of chicken embryonic intestinal villi and chicken enteroid cultures using bulk RNA-seq. Comparison of the transcriptomes of biological and technical replicate enteroid cultures confirmed their high level of reproducibility. Detailed analysis of cell subpopulation and function markers revealed that the mature enteroids differentiate from late embryonic intestinal villi to recapitulate many digestive, immune and gut-barrier functions present in the avian intestine. These transcriptomic results demonstrate that the chicken enteroid cultures are highly reproducible, and within the first week of culture they morphologically mature to appear similar to the in vivo intestine, therefore representing a physiologically-relevant in vitro model of the chicken intestine. [ABSTRACT FROM AUTHOR]

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Recently, there has been renewed interest in autologous fat grafting both for its filler and regenerative traits. The universal application, however, has been impeded by the unstable survival rates and complications. There has been substantial research undertaken on the role of adipose-derived stem cells (ADSCs) involved in fat graft fates including angiogenesis, adipogenesis, and inflammatory regulation. As the effectors of their parental cells, ADSC-derived exosomes (ADSC-exos) encapsulating multiple bioactive cargoes mediate cell-to-cell communication in a paracrine manner. ADSC-exos have received much attention for their biocompatible and efficient therapeutic potentials as "cell-free therapy" in plastic surgery, including increasing fat grafting survival rates. In this review, we summarize the current knowledge about the biological basis of ADSC-exos, ADSC-related mechanisms of fat survival, research updates of ADSC-exos in autologous fat grafting, and discuss some challenges along with research prospects. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell-derived retinal pigment epithelium (iRPE) is an attractive cell source for disease modeling and cell replacement therapy of retinal disorders with RPE defects. However, there are still challenges to develop appropriate culture conditions close to in vivo microenvironment to generate iRPE sheets, which mimic more faithfully the characteristics and functions of the human RPE cells. Here, we developed a simple, novel platform to construct authentic iRPE sheets using human amniotic membrane (hAM) as a natural scaffold. The decellularized hAM (dAM) provided a Bruch's membrane (BM)-like bioscaffold, supported the iRPE growth and enhanced the epithelial features, polarity distribution and functional features of iRPE cells. Importantly, RNA-seq analysis was performed to compare the transcriptomes of iRPE cells cultured on different substrates, which revealed the potential mechanism that dAM supported and promoted iRPE growth was the inhibition of epithelial-mesenchymal transition (EMT). The tissue-engineered iRPE sheets survived and kept monolayer when transplanted into the subretinal space of rabbits. All together, our results indicate that the dAM imitating the natural BM allows for engineering authentic human RPE sheets, which will provide valuable biomaterials for disease modeling, drug screening and cell replacement therapy of retinal degenerative diseases. Engineered RPE sheets have a great advantage over RPE cell suspension for transplantation as they support RPE growth in an intact monolayer which RPE functions are dependent on. The substrates for RPE culture play a critical role to maintain the physiological functions of the RPE in stem cell therapies for patients with retinal degeneration. In this study, we constructed engineered iRPE sheets on the decellularized human amniotic membrane scaffolds, which contributed to enhancing epithelial features, polarity distribution and functional features of iRPE. dAM exhibited the ability of anti-epithelial mesenchymal transition to support iRPE growth. Furthermore, the results of transplantation in vivo demonstrated the feasibility of iRPE sheets in retina regenerative therapy. Engineering RPE sheets on dAM is a promising strategy to facilitate the development of iRPE replacement therapy and retinal disease modeling. [Display omitted] [ABSTRACT FROM AUTHOR]

A 43-year-old man with OPA-1 autosomal dominant optic atrophy self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and sub-Tenon's injections of bone marrow–derived stem cells and within one month had developed epiretinal membranes and vitreous cells in both eyes. Purpose: The authors describe a case of new bilateral epiretinal membranes and vitreous cells after intravitreal and sub-Tenon's injections of bone marrow–derived stem cells. Methods: A case report of a 43-year-old man with OPA-1 autosomal dominant optic atrophy who self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and sub-Tenon's injections of bone marrow–derived stem cells. Results: Within one month of receiving the injections, the patient developed epiretinal membranes and vitreous cells in both eyes, seen with optical coherence tomography. Conclusion: Stem cell therapy has been gaining popularity as a potential intervention for progressive retinal and optic nerve diseases; however, the mechanism of action of bone marrow–derived stem cells is still not well understood and may result in unintended cell differentiation. [ABSTRACT FROM AUTHOR]

A 25-year-old man underwent an autologous stem cell transplant regiment for a nongermanomatous germ cell brain tumor and subsequently developed granulomatosis with polyangiitis and Purtscher's‒like retinopathy. Purpose: The authors describe a man undergoing autologous stem cell transplant, who developed granulomatosis with polyangiitis and Purtscher's‒like retinopathy. Methods: A 25-year-old man underwent fundus photography, optical coherence tomography, and fluorescein angiography to obtain a diagnosis and follow the treatment course. Results: The initial ophthalmic presentation and imaging confirmed the findings of Purtscher's‒like retinopathy. Throughout his course, he had progressive neovascularization and vitreous hemorrhages in both eyes, requiring vitrectomy and endolaser, and bevacizumab injections. Conclusion: The authors describe a patient who underwent autologous stem cell transplantation, and subsequently developed granulomatosis with polyangiitis. The presentation of Purtscher's‒like retinopathy suggests that microvascular occlusion in the retina was likely the result of granulomatosis with polyangiitis-driven vasculitis of the precapillary arterioles. [ABSTRACT FROM AUTHOR]

The dental pulp is essential in maintaining tooth homeostasis. Pulp necrosis resulting from pulpal injuries in maintaining permanent dentition may lead to irregular root growth, resulting in tooth discolouration, fracture, or even loss. Angiogenesis is generally utilised in regenerative medicine and tissue engineering, including dentistry. Researchers worldwide have spent the last two decades speeding up healing and promoting angiogenesis’ soft and hard tissue remodelling. This medical field is characterised by pathways, stem cells, signals, growth factors, receptors, and genetics. Dental implant placement, as well as soft tissue and bone regeneration using allografts, autologous grafts, and xenografts may rely on material properties for incorporation, and host response acceptance through vascularisation plays an essential role. This paper aims to review and update the possible available dental stem cells, forms of proangiogenic growth factors, and the potential curative effects of increased angiogenesis in regenerative dentistry. [ABSTRACT FROM AUTHOR]

Lupus Nephritis (LN) is a major and frequent manifestation of Systemic Lupus Erythematosus (SLE), an autoimmune disease. Renal biopsy has a pivotal role in the diagnosis, prognosis, and management of the LN. The aim of this study was to count the mesenchymal interstitial cells utilizing CD34 immunohistochemistry (IHC) and morphometric analysis, correlate them with clinical parameters, class, activity, and chronicity indices and see if it can predict the course of the disease. A total of 32 renal biopsy blocks were analyzed by H&E stain, special stains, and CD34 IHC. Microvasculature density and interstitial stem cells were highlighted by CD34. These were then counted using a previously standardized computerized digital photomicrograph system (Dewinter Optical Inc) and manual count, respectively. Out of the 32 cases, Lupus class 3 comprised of 11 (34.38%) cases, class 4 comprised of 16 (50%) cases, and mixed class 4 + 5 had 5 (15.62%) cases. It was found that CD34 expression in the microvasculature (for both microvascular density and mean vascular lumen diameter) decreased in patients of Lupus Nephritis with higher disease activity (p < 0.05). Although not statistically significant, the number of interstitial stem cells increased with lower disease activity. A statistical significance was found between serum total protein, serum albumin, and serum creatinine among the three groups of LN. Immunohistochemical staining of renal biopsy with CD34 may be used as a surrogate marker of disease activity in Lupus Nephritis patients. [ABSTRACT FROM AUTHOR]

Metastatic hepatoblastoma continues to pose a significant treatment challenge, primarily because the precise mechanisms involved in metastasis are not fully understood, making cell lines and preclinical models that depict the progression of disease and metastasis-related biology paramount. We aimed to generate and characterize a metastatic hepatoblastoma cell line to create a model for investigation of the molecular mechanisms associated with metastasis. Using a murine model of serial tail vein injections of the human hepatoblastoma HuH6 cell line, non-invasive bioluminescence imaging, and dissociation of metastatic pulmonary lesions, we successfully established and characterized the metastatic human hepatoblastoma cell line, HLM_3. The HLM_3 cells exhibited enhanced tumorigenicity and invasiveness, both in vitro and in vivo compared to the parent HuH6 cell line. Moreover, HLM_3 metastatic hepatoblastoma cells exhibited a stem cell-like phenotype and were more resistant to the standard chemotherapeutic cisplatin. This newly described metastatic hepatoblastoma cell line offers a novel tool to study mechanisms of tumor metastasis and evaluate new therapeutic strategies for metastatic hepatoblastoma. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function. To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories. PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls. While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05). Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype. [Display omitted] • Variations in early cell death differed significantly among COPD types and the control group. • Chronic bronchitis showed the lowest immune cell survival, with or without stem cells. • Adding MSCs notably boosted immune cell survival in all groups, except for emphysema. • Apoptosis increased across all COPD types compared to controls, without significant differences among the COPD types. • MSCs reduced cell death in COPD types, excluding emphysema. [ABSTRACT FROM AUTHOR]

Despite recent improvements in oncology, diagnosis, and therapy, pancreatic cancer remains extremely difficult to cure due to its aggressive growth pattern with early invasion and distant metastases, chemoresistance, and a lack of effective screening modalities for early detection. Here, novel therapeutic approaches for treating pancreatic cancer are urgently needed. Recently, stem cells have drawn a lot of interest as a possible treatment for pancreatic cancer due to their ability to locate tumors. Though research over the last few decades has revealed some very exciting and promising new treatment approaches, the clinical success of these stem-cell based anti-cancer medicines has been quite limited. The most effective stem cell-mediated therapeutic options will only be available with a deeper understanding of the intricate molecular biology underlying pancreatic cancer and the subsequent identification of cancer stem cells as a novel target that promotes the growth of the cancer and resistance to chemotherapy. This review will highlight the stem cell based anti-cancer therapy targeting pancreatic cancer stem cells and different molecular signaling pathways. A particular focus will be on the therapeutic potential of naïve Stem cells, anti-cancer drug loaded stem cells, genetically engineered stem cells and exosomal miRNA released by stem cells in pancreatic cancer treatment. Similarly, the role of nanotechnology in stem cell based anticancer therapy will be further discussed to better implementation of these cell-based cancer therapy. • Stem cell based anti-cancer therapy has promising effect to target pancreatic cancer stem cells. • Naïve, anti-cancer drug-loaded, genetically modified, and exosomal miRNA-releasing stem cells have significant therapeutic potential. • Stem cell loaded nanoparticle offers an inexpensive and effective way to develop therapeutic drugs. [ABSTRACT FROM AUTHOR]

Gene therapy is an emerging treatment for sickle cell disease that works by replacing a defective gene with a healthy gene, allowing the body to produce normal red blood cells. This form of treatment has shown promising results in clinical trials, and is a promising alternative to traditional treatments. Gene therapy involves introducing a healthy gene into the body to replace a defective gene. The new gene can be delivered using a viral vector, which is a modified virus that carries the gene. The vector, carrying the healthy gene, is injected into the bloodstream. The healthy gene then enters the patient's cells and begins to produce normal hemoglobin, the protein in red blood cells that carries oxygen throughout the body. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until December 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "Sickle Cell," "Gene Therapy" and "Stem Cell Transplantation". We explored the literature on Sickle Cell Disease for its epidemiology, etiopathogenesis, the role of various treatment modalities and the risk-benefit ratio of gene therapy over conventional stem cell transplant. Gene therapy can reduce or eliminate painful episodes, prevent organ damage, and raise the quality of life for those living with the disease. Additionally, gene therapy may reduce the need for blood transfusions and other traditional treatments. Gene therapy has the potential to improve the lives of those living with sickle cell disease, as well as reduce the burden of the disease on society. [ABSTRACT FROM AUTHOR]

Decellularized nerve allograft is an alternative to autologous nerve graft for nerve defects but has shown inferior clinical outcomes. Mesenchymal stem cells can play a key role in improving nerve regeneration of decellularized nerve allografts. The purpose of this study was to compare different mesenchymal stem cell seeding methods and to find the most efficient way to attach cells to nerve grafts for peripheral nerve regeneration. Wharton's jelly mesenchymal stem cells were collected from human umbilical cords and were seeded in the acellular nerve graft in five different ways as follows: PBS injection, fibrin glue drop, Matrigel drop, bioreactor, and Matrigel injection. A 6-mm sciatic nerve defect of Sprague–Dawley rats was bridged using mesenchymal stem cells-laden acellular nerve grafts according to the five seeding methods. Two days after implantation, the nerve tissue was biopsied and analyzed by the immunofluorescence staining of nuclei. The number of Wharton's jelly mesenchymal stem cells (+ h Nuclei) was counted in the inside, outside, and the total area of the graft sections under 200X magnification. The highest efficiency of mesenchymal stem cell attachment inside the graft and the highest total number of attached mesenchymal stem cells was observed in the group using Matrigel injection (p < 0.0001). This study showed mesenchymal stem cells can be more effectively attached to decellularized nerve graft using the injection method with Matrigel than other static or dynamic seeding methods in vivo. [ABSTRACT FROM AUTHOR]

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Background: Low-level light therapy (LLLT) is widely used for the photobiomodulation of cell behavior. Recent studies have shown that LLLT affects the proliferation and migration of various types of mesenchymal stem cells (MSCs). However, there is a lack of studies investigating the effect of LLT on enhancing the immunomodulatory properties of tonsil-derived MSCs (T-MSCs). Objective: The aim of this study was to investigate the immunomodulatory effects of conditioned media from T-MSCs (T-MSCs-CM) treated with LLLT in allergic inflammation. Methods: We isolated T-MSCs from human palatine tonsils and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM treated with LLLT was evaluated in a mouse model of allergic rhinitis (AR). We randomly divided the mice into four groups (negative control, positive control, T-MSCs-CM alone, and T-MSCs-CM treated with LLLT). To elucidate the therapeutic effect, we assessed rhinitis symptoms, serum immunoglobulin (Ig), the number of inflammatory cells, and cytokine expression. Results: We identified increased expression of immunomodulatory factors, such as HGF, TGF-β, and PGE, in T-MSCs-CM treated with LLLT, compared to T-MSCs-CM without LLLT. Our animal study demonstrated reduced allergic symptoms and lower expression of total IgE and OVA-specific IgE in the LLLT-treated T-MSCs-CM group compared to the AR group and T-MSCs-CM alone. Moreover, we found that T-MSCs-CM treated with LLLT showed significantly decreased infiltration of eosinophils, neutrophils, and IL-17 cells in the nasal mucosa and reduced IL-4, IL-17, and IFN-γ expression in OVA-incubated splenocytes compared to the AR group. Conclusions: The present study suggests that T-MSCs-CM treated with LLLT may provide an improved therapeutic effect against nasal allergic inflammation than T-MSCs-CM alone. [ABSTRACT FROM AUTHOR]

Background: The testis has been reported to be a naturally O2-deprived organ, dimethyloxaloylglycine (DMOG) can inhibit hypoxia inducible factor-1alpha (HIF-1α) subject to degradation under normal oxygen condition in cells. Objectives: The objective of this study is to detect the effects of DMOG on the proliferation and differentiation of spermatogonial stem cells (SSCs) in Bama minipigs. Methods: Gradient concentrations of DMOG were added into the culture medium, HIF-1α protein in SSCs was detected by western blot analysis, the relative transcription levels of the SSC-specific genes were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Six days post-induction, the genes related to spermatogenesis were detected by qRT-PCR, and the DNA content was determined by flow cytometry. Results: Results revealed that the levels of HIF-1α protein increased in SSCs with the DMOG treatment in a dose-dependent manner. The relative transcription levels of SSCspecific genes were significantly upregulated (p < 0.05) by activating HIF-1α expression. The induction results showed that DMOG significantly increased (p < 0.05) the spermatogenesis capability of SSCs, and the populations of haploid cells significantly increased (p < 0.05) in DMOG-treated SSCs when compared to those in DMOG-untreated SSCs. Conclusion: We demonstrate that DMOG can promote the spermatogenesis activity of SSCs. [ABSTRACT FROM AUTHOR]

The Journal of Oral Biosciences is devoted to advancing and disseminating fundamental knowledge concerning every aspect of oral biosciences. This review features review articles in the fields of "Extracellular Vesicles," "Propolis," "Odontogenic Tumors," "Periodontitis," "Periodontium," "Flavonoids," "Lactoferrin," "Dental Plaque," "Anatomy," "Induced Pluripotent Stem Cells," "Bone Cell Biology," "Dysgeusia," "Dental Caries," and "Dental Pulp Cavity," in addition to the review article by the winners of the "Lion Award" ("Sox9 function in salivary gland development") presented by the Japanese Association for Oral Biology. These reviews in the Journal of Oral Biosciences have inspired its readers to broaden their knowledge regarding various aspects of oral biosciences. The current editorial review introduces these exciting review articles. [ABSTRACT FROM AUTHOR]

Background: Intra-organic bone marrow node is predicted to be a part of the primo vascular system that plays a critical role in hematopoiesis and generation and regeneration of other cells. Two models of cell regeneration were suggested, one involving DNA synthesis and the other pertaining to DNA recycling. Objectives: The aim of this work is to extract a primo node from bone marrow, characterize its structure, understand its biochemistry and cell composition, and suggest a cell regeneration mechanism. Methods: Primo nodes were sampled from segmented halves of the rat femur. We used immunohistochemistry and high-resolution fluorescent microscopy to analyze 1200 samples obtained from 42 rats and 190 primo nodes. Results: Primo nodes in the bone marrow have an oval or round structure of about one millimeter in diameter, which is encompassed by a fine capsule, having incoming and outgoing vessels filled with the extracellular matrix and hematopoietic, mesenchymal, endothelial stem cells, as well as cells of the megakaryocyte family found in other primo nodes. Conclusion: Our findings imply that bone marrow nodes are intra-organic primo vascular nodes, and they provide ways and approaches for further investigation. Bone marrow nodes are simple to examine ex vivo in a variety of environments to assess cell regeneration mechanisms, wound healing, and organism rejuvenation and lifespan. Further research into these and other intra-organic nodes in animals and humans could lead to new regenerative medicine and longevity strategies that have yet to be discovered. [ABSTRACT FROM AUTHOR]

The aims of this study were to create Bisphonates Related Osteonecrosis of the Jaw (BRONJ) in rats and treat them with an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts). Thirty female Wistar rats were procured. Rats were labeled as Group I to III. Group I = Osteoblast group, Group II = A-Heal and Group III Control group. In Groups I-III, BRONJ was created and treated in Group I with ABMDO, Group II with A-Heal and Group III was the control group. At the end of the four weeks post treatment, all the animals were humanely killed. The intact maxillae were removed in total. Histopathological and radiological examinations were carried out with physicians blinded to the groups. Computerized tomography revealed that Groups I and II demonstrated the presence of dense osteosclerosis, intralesional calcifications, and adequate healing of the overlying soft tissues compared to Group III, which showed the presence of bone erosions at the alveolar ridge with a lack of intralesional calcifications and ulceration of the overlying soft tissues. Histologically, H&E staining Group 1 and Group 2 both showed marked reactive bone formation. Group 2 additionally revealed the most prominent vascular proliferation (also highlighted by Factor VIII, an endothelial cell marker) among all groups. Group 3 showed cartilaginous proliferation with less reactive bone formation, implicating decreased endochondral ossification compared to Groups 1 and 2. This study shows that angiogenesis factor (A-Heal) and ABMDO were successful in the treatment of experimentally created BRONJ in an animal model. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by adjuvant chemotherapies and surgical approaches. However, poor prognosis often occurs among osteosarcoma patients due to recurrence, metastasis, or drug resistance problems. Cancer stem cells (CSCs), a specific type of tumor malignant cells with stem cell-like properties, have been reported to be responsible for tumor origination, aggression, metastasis, recurrence, and drug resistance. CSCs have been identified in osteosarcomas treatment, which exhibits self-renewal, multi-potency, and enhanced drug resistance. Therefore, in the present narrative review, we intend to summarize the role of lncRNAs in regulating CSCs and their effectiveness in the treatment of osteosarcoma. MATERIALS AND METHODS: The databases PubMed (Medline), Web of Science, Embase, Scopus, and Cochrane Library, were used for the presented study. The keywords we used to complete our search are 'lncRNA', 'Stem cell', and 'osteosarcoma'. A total of over 800 relevant articles, with a time limit from 2010 to 2021, were identified according to search strategy. Duplicate records and review articles were excluded by their titles and abstracts. Finally, we found about 80 articles matching our inclusion criteria, which included about 13 relevant studies focusing on both the mechanism and effectiveness of osteosarcomas treatment among osteosarcoma patients. RESULTS: CD133, CD117, ALDH, and Stro-1 are validated as the stem cell biomarkers in osteosarcoma CSCs. Accumulating evidence has revealed that lncRNAs, containing HIF2PUT, SOX2-OT, MALAT1, THOR, B4GALT1-AS1, H19, PVT1, FER1L4, LINK-A, DANCR, and DLX6-AS1, play a potential role in regulating CSCs in osteosarcoma. The drug resistance, inhibition of the relapse, and metastasis in osteosarcoma could be avoided via regulating lncRNAs of targeting CSCs. CONCLUSIONS: Multiple lncRNAs regulate CSCs in osteosarcoma via various molecular mechanisms. This review demonstrated that the method of eliminating CSCs by targeting these lncRNAs is a safe, effective, and a well-tolerated way for osteosarcoma patients, which shows a broad research prospect in tumor diagnoses and therapies. However, this method should be further demonstrated by better animal models and more clinical experiments. [ABSTRACT FROM AUTHOR]

The mechanical properties of the native extracellular matrix play a key role in regulating cell behavior during developmental, healing and homeostatic processes. Since these properties change over time, it may be valuable to have the capacity to dynamically vary the mechanical properties of engineered hydrogels used in tissue engineering strategies to better mimic the dynamic mechanical behavior of native extracellular matrix. However, in situ repeatedly reversible dynamic tuning of hydrogel mechanics is still limited. In this study, we have engineered a hydrogel system with reversible dynamic mechanics using a dual-crosslinkable alginate hydrogel. The effect of reversible mechanical signals on encapsulated stem cells in dynamically tunable hydrogels has been demonstrated. In situ stiffening of hydrogels decreases cell spreading and proliferation, and subsequent softening of hydrogels gives way to an increase in cell spreading and proliferation. The hydrogel stiffening and softening, and resulting cellular responses are repeatedly reversible. This hydrogel system provides a promising platform for investigating the effect of repeatedly reversible changes in extracellular matrix mechanics on cell behaviors. Since the mechanical properties of native extracellular matrix (ECM) change over time during development, healing and homeostatic processes, it may be valuable to have the capacity to dynamically control the mechanics of biomaterials used in tissue engineering and regenerative medicine applications to better mimic this behavior. Unlike previously reported biomaterials whose mechanical properties can be changed by the user only a limited number of times, this system provides the capacity to induce unlimited alterations to the mechanical properties of an engineered ECM for 3D cell culture. This study presents a strategy for on-demand dynamic and reversible control of materials' mechanics by single and dual-crosslinking mechanisms using oxidized and methacrylated alginates. By demonstrating direct changes in encapsulated human mesenchymal stem cell morphology, proliferation and chondrogenic differentiation in response to multiple different dynamic changes in hydrogel mechanics, we have established a repeatedly reversible 3D cellular mechanosensing system. This system provides a powerful platform tool with a wide range of stiffness tunability to investigate the role of dynamic mechanics on cellular mechanosensing and behavioral responses. [Display omitted] [ABSTRACT FROM AUTHOR]

En coup de sabre deformity (ECDS) is a form of localized scleroderma in the frontoparietal region caused by progressive subcutaneous tissue atrophy and bony defect. Although ECDS involves two layers, skin/subcutaneous tissue and bone, the existing literature mainly focuses only on treating the skin/subcutaneous tissue layer. In this case series, we aimed to propose a novel approach that includes the combined use of fat grafting and demineralized bone matrix (DBM). Four patients with ECDS deformity, operated between February 2016 and October 2018, were retrospectively evaluated. All the patients were treated with the novel approach. Patients were evaluated with localized scleroderma scale and computed tomography (CT) scan in the preoperative period and at the annual follow-up. We observed remarkable improvement in the localized scleroderma scale including appearance, palpation, and size scores in all patients at the annual follow-up. CT scans at the annual follow-up revealed new callus formation at the bony defect area in all patients. Reinforcing fat grafting with DBM could promote healing of the bony and skin/subcutaneous tissue defects associated with ECDS. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that the sustained release of ions from dental restorative materials have acid buffering capacity, prevents tooth enamel demineralization, and inhibits bacterial adhesion. Herein, the release behavior and bioresponsiveness of ions released from surface pre-reacted glass-ionomer (S-PRG) fillers were investigated in different types of media based on human dental pulp-derived stem cell (hDPSC) responses. The hDPSCs were cultured for 1-7 days in S-PRG eluates diluted with varying amounts of cell culture media. S-PRG released several types of ions, such as F-, Sr2+, Na+, Al3+, BO3 3-, and SiO3 2-. The balance of eluted ions differed depending on the dilution and solvent, which in turn affected the cytotoxicity, cell morphology, cell proliferation, and alkane phosphatase activity of hDPSCs, among other properties. The results suggest that tailored S-PRG filler eluates could be designed and prepared for application in dental practice. [ABSTRACT FROM AUTHOR]

As an indispensable component of the extracellular matrix, perlecan (Pln) plays an essential role in cartilaginous tissue function. Although there exist studies suggesting that Pln expressed by cartilaginous tissues is critical for chondrogenesis, few papers have discussed the potential impact Pln may have on cartilage regeneration. In this review, we delineate Pln structure, biomechanical properties, and interactive ligands—which together contribute to the effect Pln has on cartilaginous tissue development. We also review how the signaling pathways of Pln affect cartilage development and scrutinize the potential application of Pln to divisions of cartilage regeneration, spanning vascularization, stem cell differentiation, and biomaterial improvement. The aim of this review is to deepen our understanding of the spatial and temporal interactions that occur between Pln and cartilaginous tissue and ultimately apply Pln in scaffold design to improve cell-based cartilage engineering and regeneration. As a key component of the basement membrane, Pln plays a critical role in tissue development and repair. Recent findings suggest that Pln existing in the pericellular matrix surrounding mature chondrocytes is actively involved in cartilage regeneration and functionality. We propose that Pln is essential to developing an in vitro matrix niche within biological scaffolds for cartilage tissue engineering. Perlecan's potential application in cartilage regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

There are no human cancer cell lines of external auditory canal origin available for research use. This report describes the establishment of a culture condition for external auditory canal squamous cell carcinoma, derived from human tumor tissue. Successive squamous cell carcinoma colonies were dissociated by trypsin, subcultured, and maintained on a feeder layer (MMC‐TIG‐1‐20), yielding a clonally proliferating cell culture. Two morphological types of colony were observed: (a) densely packed colonies and (b) colonies with indistinct boundaries characterized by cell–cell complexes with fibroblast feeder cells. The SCC‐like characteristics of these cells were evidenced by positivity for p53, SCCA1/2, cytokeratin, and vimentin, and cancer stem cell properties were indicated by positivity for CD44, CD133, Oct3/4, and alkaline phosphatase (ALP). One of the unique properties of cell cultures is their tendency to form steric colonies in vitro on feeder layer cells. In addition, in the presence of fresh macrophages, the cells very slowly transform to break away from colonies as free cells, a process that resembles the epidermal–mesenchymal transition, whereby cell–cell interactions are weakened and migration activity is enhanced. These factors are purported to play a key role in cancer cell metastasis. [ABSTRACT FROM AUTHOR]

This study aims to investigate the utility of mesenchymal stem cells (MSCs) applied as an epicardial patch during coronary artery bypass graft (CABG) to target hibernating myocardium; that is, tissue with persistently decreased myocardial function, in a large animal model. Hibernating myocardium was induced in juvenile swine (n = 12) using a surgically placed constrictor on the left anterior descending artery, causing stenosis without infarction. After 12 weeks, single-vessel CABG was performed using left internal thoracic artery to left anterior descending artery graft. During CABG, an epicardial patch was applied to the hibernating myocardium region consisting either of MSCs grown onto a polyglactin mesh (n = 6), or sham polyglactin mesh without MSCs (n = 6). Four weeks after CABG and patch placement, cardiac magnetic resonance imaging was performed and cardiac tissue was examined by gross inspection, including coronary dilators for vessel stenosis and patency, electron microscopy, protein assays, and proteomic analysis. CABG + MSC myocardium showed improvement in contractile function (78.24% ± 19.6%) compared with sham patch (39.17% ± 5.57%) during inotropic stimulation (P <.05). Compared with sham patch control, electron microscopy of CABG + MSC myocardium showed improvement in mitochondrial size, number, and morphology; protein analysis similarly showed increases in expression of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (0.0022 ± 0.0009 vs 0.023 ± 0.009) (P <.01) along with key components of the electron transport chain, including succinate dehydrogenase (complex II) (0.06 ± 0.02 vs 0.14 ± 0.03) (P <.05) and adenosine triphosphate synthase (complex V) (2.7 ± 0.4 vs 4.2 ± 0.26) (P <.05). In hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function. [Display omitted] [ABSTRACT FROM AUTHOR]