Background: The aim of this study was to develop a novel biocompatible composite for the regeneration of damaged dental pulp tissue. Materials and Methods: To create the composite, porous microcarriers were loaded with freeze-dried bone marrow stem cells and embedded in a fibrinogen-thrombin gel. The regenerative potential of the composite was evaluated in both ectopic and orthotopic animal models of dental pulp injury. Results: The composite stimulated the migration and proliferation of host pulp cells via growth factors and cytokines secreted by freeze-dried bone marrow stem cells. Furthermore, the microcarrier-based scaffold created a three-dimensional microenvironment that preserved the paracrine activity of stem cells, promoting the effective regeneration of damaged or partially amputated dental pulp. Conclusion: This bioactive composite demonstrates significant potential for regenerative endodontics, facilitatingthe restoration of dental pulp. Further studies are needed to elucidate the specific role of paracrine factors from freeze-dried stem cells in improving pulp tissue regeneration.
Background: Growth differentiation factor 11 (GDF11) has emerged as a potential regulator of bone regeneration; however, the molecular mechanisms through which it influences osteogenic differentiation, particularly in relation to mitochondrial quality control, remain unclear. This study aimed to elucidate the role of adenosine monophosphate-activated protein kinase (AMPK)-dependent mitophagy in GDF11-mediated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMMSCs). Methods: rBMMSCs were induced toward osteogenic differentiation with or without GDF11 treatment. To specifically inhibit AMPK-dependent mitophagy, Compound C, an AMPK inhibitor, was employed. Osteogenic differentiation was evaluated using alkaline phosphatase (ALP) staining and activity assays, while Alizarin Red S (ARS) staining was performed to assess matrix mineralization. The expression of Mitophagy- and osteogenesis-associated markers was analyzed through immunofluorescence staining, quantitative real-time PCR, and western blotting. Results: GDF11 significantly enhanced the osteogenic differentiation of rBMMSCs, as evidenced by increased ALP activity, more intense ALP staining, enhanced calcium nodule formation, and elevated expression of ALP and RUNX2. GDF11 activated mitochondrial function by promoting AMPK phosphorylation and inducing Mitophagy. Inhibition of AMPK significantly impaired Mitophagy, while Compound Cmediated blockade of AMPK-dependent mitophagy not only suppressed basal osteogenic differentiation but also abolished the pro-osteogenic effects of GDF11. This was reflected by a pronounced reduction in GDF11-induced ALP activity, mineralization, and the expression of key osteogenic genes at both the mRNA and protein levels. Conclusion: GDF11 enhances the osteogenic differentiation of rBMMSCs by activating AMPK-dependent mitophagy. These findings identify AMPK-dependent Mitophagy as a pivotal mechanism mediating the osteogenic actions of GDF11, providing new mechanistic insights that may guide the development of novel strategies for bone regeneration.
This report describes two women aged 45 and older who achieved live births following intraovarian administration of a novel combination of mechanically processed adipose nanofat rich in adipose-derived stem cells (ADSCs) and autologous platelet-rich plasma (PRP). Both patients had a history of prolonged infertility and multiple failed assisted reproductive technology cycles with in vitro fertilization (IVF). Case 1, a 46-year-old with diminished ovarian reserve and prior miscarriage, underwent adipose-PRP treatment after unsuccessful minimal stimulation IVF. Six months later, she conceived naturally and delivered a healthy infant at age 47. Case 2, a 45-year-old with endometriosis and multiple failed IVF attempts, conceived via frozen embryo transfer of her only euploid embryo produced three months after adipose-PRP treatment, resulting in the birth of a healthy infant. The combination approach was developed to comply with U.S. FDA minimal manipulation guidelines, avoiding enzymatic processing of adipose tissue. This report is, to our knowledge, the first to document natural conception in women with age over 45 following combined adipose nanofat ADSCs and PRP intraovarian injection, and among the few to describe live births at this age using autologous oocytes after such therapy. These findings suggest that adipose-PRP treatment may offer a promising regenerative option for women with extremely diminished ovarian reserve who desire genetically related offspring, though controlled studies are required to confirm long term safety, efficacy, and appropriate patient selection.
BACKGROUND:The ovarian surface epithelium (OSE) stem cells are crucial components of the human ovary and play a significant role in both the reproductive function and ovulatory wound repair. Harnessing these stem cells could provide a novel therapeutic strategy for reproductive disorders. METHODS:In this study, we determine and compare the differentiation potential of OSE stem cells into Oocyte-like cells between human and mice-derived OSE stem cells. In addition, we assessed OSE cellular characteristics associated with their stemness and self-renewal abilities and demonstrated their capacity for in vitro differentiation. RESULTS:We found that the ovarian surface epithelium harbored putative stem cells characterized by Alkaline Phosphatase (AP) activity, cell proliferation, expression of mesenchymal lineage surface markers, and pluripotent transcriptional markers. Interestingly, human-derived OSE stem cells exhibited increased AP activity and cell proliferation compared to mouse OSE stem cells, suggesting high levels of self-renewal and differentiation potential. Moreover, our evaluation of the in vitro differentiation potential into Oocyte-like cells for human or mouse OSE stem cells demonstrated an enhanced oogenesis potential for human OSE stem cells compared to mouse OSE cells, as evidenced by the analysis of germ cell marker expression and the production of Oocyte-like cells. CONCLUSION:Our data highlighted the difference in the characterization and differentiation potential into Oocyte-like cells between human-derived OSE stem cells and mouse-derived OSE stem cells and lay a foundation for a future establishment of stem cell line with implications for reproductive cell therapy. In the realm of reproductive medicine, infertile patients with nonfunctional ovaries represent a significant area of interest, and any potential to regenerate their ovaries would hold great importance.
OBJECTIVE:The aim of this study was to identify the different immune-related genes (DIRGs) of mesenchymal stem cells (MSCs) in three-dimensional (3D) vs. two-dimensional (3D) environment. MATERIALS AND METHODS:The gene expression dataset GSE52896 was downloaded from the Gene Expression Omnibus (GEO) database. We obtained immune-related genes from the ImmPort database. The array was processed with the R language to obtain differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed with the STRING database and analyzed with Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data were performed with DAVID (https://davidbioinformatics.nih.gov/). We constructed a least absolute shrinkage and selection operator (LASSO) regression model and multiple support vector machine - recursive feature elimination (mSVM-RFE) model to identify the key DIRGs in cells growing in 3D culture. The performance of the key genes was validated in the GSE58919 dataset. Western blot analysis was performed to verify the expression of one key gene, Cysteine and Glycine Rich Protein 1 (CSRP1). Key immune-related genes were identified using CIBERSORT (https://cibersortx.stanford.edu/). RESULTS:A total of 446 DEGs were screened under two different culture conditions (2D and 3D), and 65 DEGs were identified. GO analysis revealed changes in inflammatory response, extracellular region, and protein binding. KEGG enrichment analysis showed that the DEGs were enriched in pathways involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors and the TNF signaling pathway. Seven key genes were obtained from the intersection of the outputs of the LASSO and mSVM-RFE algorithms. The expression of the seven key genes was verified in the GSE52896 dataset. Western blot (WB) confirmed the alteration of CSRP1 expression under different culture conditions. CONCLUSION:Stem cells showed significant changes in immune response gene expression under 3D culture conditions. CSRP1 plays essential roles in MSC immunomodulation.
OBJECTIVE:Fibronectin 1 (FN1) encodes fibronectin, a protein essential for cell adhesion, migration, extracellular matrix assembly, and regulation of cell differentiation and proliferation. While FN1 has been implicated in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its role in neural differentiation remains unclear. This study aimed to investigate the effect of FN1 gene interference on neural differentiation of human BMSCs and explore the underlying molecular mechanisms. METHOD:Three small interfering RNAs (ssi-417, si-4467 and si-5468) targeting FN1 were designed and transfected into BMSCs undergoing neural differentiation. Morphological changes were observed, and FN1 expression was assessed at both mRNA and protein levels. Alkaline phosphatase (ALP) staining was performed, and the expression of neural differentiation-related markers (MAP2, Tuj1, NSE and DCX) was quantified. Transcriptome sequencing was used to identify differentially expressed genes (DEGs), alternative splicing (AS) events and key pathways. Protein-protein interaction (PPI) network analysis was conducted to identify hub genes. RESULT:Cells in the FN1 interference group retained a spindle-shaped mesenchymal morphology. FN1 expression at both mRNA and protein levels was significantly reduced in all three siRNA groups compared with the model group (P < 0.05). ALP staining showed a higher positive rate in the FN1 interference group. Expression of neural differentiation markers (MAP2, Tuj1, NSE and DCX) was significantly downregulated in the interference group compared with the model group (P < 0.05). Transcriptome analysis revealed 1047 upregulated and 1077 downregulated DEGs, enriched in pathways related to signal transduction, immune response, RNA processing, apoptosis and DNA repair. Additionally, 2246 alternative splicing events were identified, and PPI network analysis highlighted IL-6 as a core gene. CONCLUSION:FN1 gene interference inhibits neural differentiation of BMSCs and alters key signaling pathways and splicing patterns, suggesting that FN1 plays a critical role in regulating stem cell fate. These findings provide new insights into the molecular mechanisms underlying neural differentiation of BMSCs.
BACKGROUND:Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction, with chronic inflammation playing a central pathogenic role. Mesenchymal stem cells (MSCs) possess therapeutic potential through immunomodulatory and tissue-reparative properties. This study aimed to evaluate the safety and efficacy of intravenous allogeneic umbilical cord-derived MSCs (UC-MSCs) in patients with T2DM. METHODS:Eleven adults with T2DM (disease duration ≥ 10 years; HbA1c ≤ 8%) received a single intravenous infusion of 1 × 108 UC-MSCs. This open-label pilot trial assessed safety (adverse events, hematologic and metabolic parameters) and efficacy (glycemic control and inflammatory gene expression) over a 2-month follow-up period. UC-MSCs were isolated under standardized conditions. RESULTS:UC-MSC transplantation in patients with T2DM was well tolerated, with only transient fever (36.3%) and mild muscle pain (18.2%) reported. The intervention resulted in significant metabolic improvements, including a 2.1% reduction in HbA1c (P = 0.00095) and a decrease in fasting glucose by 93.7 mg/dL (P = 0.00097). Treatment also modulated inflammatory pathways, as evidenced by upregulating of IKBα (1.76-fold, P = 0.0067) and downregulating of TNFα (0.62-fold) and IL-6 (0.65-fold). Variability in IKBα expression accounted for 48% of the variance in HbA1c (r = -0.69). Two distinct response patterns were observed: improvement in insulin sensitivity (7/11) via NF-κB suppression, and enhancement of β-cell function (3/11). CONCLUSION:Allogeneic UC-MSC transplantation appears safe and significantly improves glycemic control in patients with T2DM. The heterogeneity in patient responses underscores the importance of stratification based on inflammatory status. These findings support UC-MSC therapy as a promising disease-modifying strategy and highlight the need for larger, controlled clinical trials.
BACKGROUND:Liver diseases remain a major global health burden, with limited treatment options for advanced hepatic dysfunction. Stem cell-based therapies offer a favorable strategy for liver regeneration by providing a renewable source of functional hepatocyte-like cells (HLCs). This study aims to investigate the effect of Fibroblast growth factor (FGF) and Insulin-like Growth Factor (IGF) pre-treatment on the differentiation capacity of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) and their potential application in regenerative therapy for liver fibrosis or cirrhosis. METHODS:Cell viability was evaluated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal violet, and trypan blue assays. For the assessment of differentiation potential, ELISA (Enzyme-Linked Immunosorbent Assay) and Immunocytochemistry of Hepatocyte Growth Factor (HGF) and Epidermal Growth Factor (EGF) were performed. For angiogenesis, an ELISA of Vascular Endothelial Growth Factor (VEGF) was performed. For apoptosis, an ELISA of p53 was performed. Gene expression analysis of differentiation markers, including Cytochrome P450 Family 1 Subfamily A Member 2 (CYP1A2), Cytochrome P450 Family 3 Subfamily A Member 2 (CYP3A2), Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF), Alkaline Phosphatase (ALP), Alpha-Fetoprotein (AFP), and albumin, was also performed. Furthermore, antioxidant enzymes were also measured. RESULTS:UC-MSCs preconditioned with FGF and IGF exhibited significantly enhanced viability and reduced cell death, as confirmed by MTT, crystal violet, and trypan blue assays. ELISA and immunocytochemistry demonstrated marked upregulation of hepatic markers (HGF, EGF), angiogenic factor (VEGF), and reduced expression of the apoptotic marker p53 in the preconditioned groups. The gene expression analysis confirmed superior regenerative potential in the FGF+IGF-treated group. Antioxidative analysis further validated a higher level of antioxidative potential in preconditioned cells. CONCLUSION:Preconditioned UC-MSCs offer a promising cell-based alternative to liver transplantation by enhancing regeneration, reducing apoptosis, and promoting angiogenesis and antioxidant defense in damaged liver tissue.
AIM:Amyotrophic lateral sclerosis (ALS), Lewy Body dementia (LBD), Kennedy disease (KD), and Congenital Myasthenic Syndrome (CMS) are progressive motor disorders for which no disease modifying treatment exists. ALS and LBD are uniformly, and often rapidly, fatal. No treatment of any kind has ever resulted in actual improvement for ALS patients; the best that has been achieved is minor slowing of their progression. Forty-one preclinical studies of intra-nasal instillation of mesenchymal stem cell exosomes have, however, demonstrated complete safety and efficacy for models of a variety of neurocognitive and motor disorders. We hypothesized that intranasal exosomes treatment in humans would be completely safe and also effective for the treatment of motor disorders such as ALS, LBD, KD and CMS. METHODS:18 patients with ALS, Kennedy Disease, Congenital Myasthenic Syndrome, or Lewy Body Dementia had 32 AlloEx Exosome® treatments to assess safety, attenuation of disease, and increase in strength and motor function. The study was conducted under the clinical trial NCT07105371 found at clinicaltrials.gov/study/NCT07105371. RESULTS:There were no adverse events of any kind reported among these treatments. All patients, except for one, achieved some degree of clinical and strength improvement; the longest improvement was recorded at the 6-month follow-up. CONCLUSION:Intranasally-instilled AlloEx Exosomes® are completely safe, attenuate progression, and improve strength in ALS, Kennedy Disease, CMS, and LBD.
Stem cell therapy is revolutionizing the treatment of neurological disorders, offering innovative approaches for regeneration and repair. This paper explores five distinct mechanisms of stem cell therapy, focusing on their applications and therapeutic potential. Neural stem cells (NSCs) combined with pharmacological agents, such as FTY720, enhance remyelination and neural repair in multiple sclerosis (MS) and spinal cord injuries (SCI). Induced pluripotent stem cells (iPSCs) provide a personalized approach by enabling the generation of patient-specific NSCs for treating conditions like Parkinson's Disease (PD). Gene-editing technologies, such as CRISPR-Cas9, expand the scope of NSC applications by facilitating precise interventions for genetic disorders like SMARD1. Neurotrophic factors derived from NSCs present a cell-free alternative to promote neuronal survival and repair in diseases such as Parkinson's and Huntington's disease. Additionally, NSC-derived extracellular vesicle therapies, such as intranasal delivery methods for AD treatment, offer non-invasive approaches to reduce neuroinflammation and enhance cognitive recovery. While these mechanisms demonstrate remarkable therapeutic potential, challenges such as cost, scalability, and safety remain. This review provides a comprehensive analysis of these mechanisms, highlighting their contributions to the future of regenerative medicine and personalized therapeutic strategies.
Stem cells possess self-renewal and multipotent differentiation capabilities, exhibiting broad applications in regenerative medicine and tissue homeostasis maintenance. Their fate regulation relies heavily on precise epigenetic mechanisms. Cancer stem cells (CSCs), as key drivers of tumor heterogeneity, recurrence, and drug resistance, share extensive epigenetic features with normal stem cells, forming a complex and dynamic regulatory network. Mechanisms including DNA methylation, histone modification, chromatin remodeling, and ncRNAs collectively sustain stem cell pluripotency and tumor stemness, while aberrant epigenetic alterations serve as core drivers of tumor initiation and progression. In recent years, with the advent of single-cell omics and CRISPR-dCas9 epigenetic editing technologies, epigenetic "crosstalk" between stem cells and tumor cells has been progressively uncovered, especially the multidimensional epigenetic reprogramming induced by the tumor microenvironment (TME) that promotes CSC traits and drug resistance. This review systematically summarizes the epigenetic regulatory mechanisms of stem cells, epigenetic abnormalities in tumors, their interactions, and translational potential in therapeutic strategies, focusing on frontier topics such as reversible epigenetic plasticity, metabolic-epigenetic interplay, and liquid biopsy epigenetic biomarkers. Looking forward, artificial intelligence (AI) and big data analysis are expected to deepen the understanding of epigenetic heterogeneity, driving integrative innovations in precision medicine and regenerative interventions. Comprehensive understanding of the epigenetic crosstalk between stem cells and tumors will provide solid theoretical support and technical pathways for CSC-targeted therapies, epigenetic drug development, and stem cell fate manipulation.
BACKGROUND:Epigenetic modifiers play an important role in regulating the fate of hematopoietic stem cells (HSCs). The chromatin-modifying agents (CMA) have previously been shown to expand HSCs from cord blood (CB) and bone marrow (BM) CD34+ cells. Meanwhile, DNA methylation maintains persistent cellular memories and is thought to be the primary epigenetic barrier to reprogramming. The DNA hypomethylation drug decitabine is one of the CMA that could alter gene expression and HSC self-renewal. It has been reported that decitabine could promote platelets generation in ITP patients. OBJECTIVE:It's unknown if decitabine could affect CD34+ cells and megakaryocytes generation and maturation from human induced pluripotent stem cells (hiPSCs). METHODS:We utilized serum free, exon free and feeder free differentiation system to generate CD34+ from hiPSCs and induced them differentiation into megakaryocytes. Different concentrations of decitabine were added at different stages and analyzed these cells by RT-PCR, flow cytometry analysis, cell counting and other regular experimental methods. RESULTS:The proliferation and function of CD34+ cells in vitro were significantly suspended after exposure to decitabine. Low concentration of decitabine could maintain the CD34+ function. In addition, we found that decitabine did not have any effect on the megakaryocyte generation, but it prevented megakaryocyte maturation. The DNA methyltransferases (DNMTs) changed a lot not only in CD34+ stage but also in the megakaryocyte generation and maturation due to decitabine addition. CONCLUSIONS:These results suggested that the effect of decitabine on CD34+ cells from hiPSCs was very different from CB, PB and BM CD34+ cells and the epigenetic changes may play an important role in the CD34+ expansion and megakaryocytes maturation. It may provide a potential mechanism of studying hiPSCs derived HSCs and megakaryocytes maturation in the future.
Hearing loss is a prevalent organ-specific disorder affecting individuals throughout their lifespan, with over 466 million cases reported globally. The conditions can be classified into two broad categories: hereditary and nonhereditary. HHL, caused by genetic mutations or chromosomal abnormalities, can be divided into nonsyndromic (NSHL) and syndromic (SHL) subtypes. NSHL presents as isolated auditory impairment without systemic manifestations, whereas SHL involves concurrent dysfunction in other organ systems. Nonhereditary hearing loss typically results from infections, ototoxic drugs, noise exposure, trauma, or age-related degeneration. Current clinical interventions focus on symptom management through hearing aids and cochlear implants, as no curative treatment exists for genetic forms. Recent studies have shown the therapeutic potential of gene therapy in animal models of genetic deafness, although clinical translation faces challenges, including viral vector safety, transfection efficiency, and target specificity. This systematic review synthesizes current progress in gene therapy for HHL and evaluates barriers to clinical implementation, offering insights for future translational studies.
OBJECTIVES:To evaluate the in vivo developmental and therapeutic potential of a novel parthenogenetic embryonic stem cell line (NF-pES), which contains genomes from both non-growing and grown oocytes. METHODS:NF-pES cells were injected into mouse blastocysts to generate chimeric mice, and their contribution to various tissues was assessed. Skeletal muscle differentiation potential was examined through teratoma assays and analysis of muscle tissue in chimeric mice. For therapeutic assessment, a skeletal muscle injury model was established by cardiotoxin and irradiation treatment of the tibialis anterior muscle. NF-pES-derived precursor cells, obtained through in vitro induction and differentiation, were transplanted into the injured muscle. RESULTS:Notably, NF-pES cells contributed extensively to multiple somatic lineages in chimeric mice, with high levels of chimerism observed in the heart (83.36%) and bone marrow (50.44%). These levels are comparable to those achieved with embryonic stem cells derived from fertilized embryos. Importantly, NF-pES cells demonstrated robust myogenic differentiation capacity, as evidenced by their contribution to skeletal muscle tissues in both teratoma formation assays and in vivo chimeric muscle integration. Following in vitro induction, NF-pES-derived precursors were transplanted into the injured tibialis anterior muscle of recipient mice to assess their regenerative potential in vivo. One month after transplantation, immunohistochemical analysis confirmed the successful engraftment of donor-derived cells within the host muscle tissue. These donor-derived cells expressed markers of terminal myogenic differentiation and were incorporated into mature skeletal muscle fibers. CONCLUSIONS:NF-pES cells exhibit strong developmental capacity and therapeutic potential for skeletal muscle regeneration, suggesting their value in future regenerative medicine applications.
The association of bone marrow stem cells (BMSCs) with cardiac function outcomes and treatment outcomes in heart failure (HF) patients with low ejection fraction (EF) has been heterogeneous across studies. This systematic review aimed to investigate the effect of BMSCs on functional, clinical, quality of life, and major adverse cardiovascular events (MACE) outcomes in HF patients with low EF. PubMed, Scopus, Clinicaltrial.gov, Cochrane Library, Google Scholar, and Web and reference databases were searched for articles that examined the effect of BMSCs therapy on improving cardiac outcomes in patients with low EF, from 2000 to 2024. Differences in left ventricular ejection fraction (LVEF), MACE, echocardiographic indices (left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV)), 6-min walk test (6-MWT), New York Heart Association (NYHA) class and immunologic responses were defined as outcomes. Low EF was defined as an EF <45%. Finally, 14 RCTs involving 710 HF patients with low EF were included. BMSCs transplantation was associated with improvements in echocardiographic parameters, EF rate, and NYHA class in most studies (9 of 14) compared to the control group, regardless of the time of outcome assessment (3 or 6 months). It also significantly improved the 6-MWT in most studies. Improvements in parameters and functional outcomes were similar at both evaluation periods, 6 and 12 months. The BMSCs transplantation was not significantly associated with the incidence of MACE and immunological responses. The results of this systematic review supported the positive role of BMSCs transplantation in improving echocardiographic parameters, EF rate, NYHA class, and 6-MWT in HF patients with low EF. BMSCs transplantation was not significantly associated with the incidence of MACE and immunological responses.
Mesenchymal stem cells (MSCs) are a type of pluripotent stem cells originating from the mesoderm, known for their capability to differentiate into various specific tissue cell types and fulfill corresponding physiological roles. Furthermore, MSCs are essential in modulating the tissue microenvironment through the release of soluble factors that can modify the local inflammatory conditions of injured tissues. As a result, MSCs show considerable promise for therapeutic use in a range of traumatic scenarios, including but not limited to liver damage, myocardial infarction, neurological conditions, lung trauma, kidney injuries, and disorders affecting the female reproductive system. They play a key role in alleviating cell apoptosis, sustaining cell survival, encouraging proliferation, enhancing the inflammatory milieu, minimizing tissue fibrosis, and supporting vascular regeneration. These mechanisms are crucial for controlling excessive and persistent inflammatory reactions that arise after organ injury, which may lead to cell death and hindered blood circulation, ultimately causing fibrosis and weakened organ functionality. Additionally, MSCs are gradually being incorporated into clinical settings, where careful considerations regarding methods of administration, dosing, safety, and effectiveness are vital for achieving optimal clinical results. This review provides an overview of the mechanisms by which mesenchymal stem cells aid in the repair of major bodily organs. We also examine their current status, obstacles, and pertinent issues concerning clinical applications.
Human melanocytes (MCs) and melanocyte stem cells (McSCs) are integral to skin pigmentation and appendage pigmentation, originating embryonically from neural crest cells. In adult skin, McSCs residing in the epidermis sustain the continuous regeneration of functional melanocytes, a process vital for skin homeostasis and repair. Advances in McSC research have unravelled their pivotal roles in combating disorders such as vitiligo, hair greying, impaired wound healing, and melanoma. Previous studies have significantly advanced our knowledge of the cellular and molecular characteristics of this unique stem cell population. However, a comprehensive understanding of their characteristics in melanocyte dysfunctions leading to conditions like vitiligo is still lacking. Dysfunction or depletion of McSCs is linked to these conditions, highlighting their significance in maintaining skin health. Cutting-edge technologies like single-cell RNA sequencing, spatial transcriptomics, gene editing, and whole-genome sequencing have deepened our understanding of McSC biology and their regulatory microenvironment. This review delves into the latest discoveries, offering a comprehensive perspective on McSCs and their therapeutic potential. By identifying specific molecular signals and crosstalk mechanisms, McSC research opens avenues for regenerative medicine applications, including skin repigmentation, tissue repair, and cancer treatment. The field's progression sets the stage for transformative breakthroughs in skin regeneration and broader regenerative therapies.
Cisplatin and oxaliplatin are among the most extensively used anti-cancer drugs in the treatment of various types of cancer. However, the cytotoxicity associated with these drugs in normal and adult stem cells is a major concern. OBJECTIVES:This study aimed to determine the oxidative stress induced by platinum drugs in murine mesenchymal stem cells (mMSCs). METHODS:mMSCs were cultured and treated with cisplatin and oxaliplatin concentrations (5 μM, 15 μM, and 25 μM/L) for 1, 4, 24, 48, and 72 hours. Morphological changes and viability of cells were observed. Oxidative stress was assessed by the expression of 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Necroptosis was determined by Acridine Orange/Ethidium Bromide (AO/EB) staining. Moreover, mRNA levels of DNA repair genes, particularly genes involved in mismatch repair (MMR), including MLH3, MSH2, MLH1, MSH6, and PMS2, and nucleotide excision repair (NER) pathways, such as ERCC1 were measured using Taq-Man Quantitative Real-Time Polymerase Chain Reaction (TaqMan-qRT-PCR). RESULTS:The proliferation and morphology of mMSCs were noticeably influenced by cisplatin and oxaliplatin at 25 μM, compared to 5 μM and 15 μM by 72 hours. 8OHdG positive and necroptotic cells were significantly (P < 0.001) high from 24 to 72 hours among 25 μM drug-treated mMSCs. The concentration and temporal oxidative stress generated in mMSCs by cisplatin and oxaliplatin disturbed the expression of DNA repair genes at the mRNA level (P < 0.001). Cisplatin remarkably upregulated the expression of MLH1 and PMS2 (≥ 3.0-fold) at 24 hours, while it downregulated MSH2, MLH1, MSH6, and PMS2 (≤ 0.5-fold) at 72 hours. However, oxaliplatin noticeably caused the upregulation of MLH3 and ERCC1 expression (≥ 3.0-fold) at 24-48 hours, and downregulation of MSH2, MLH1, MSH6, PMS2, and ERCC1 (≤ 0.5-fold) at 72 hours. CONCLUSIONS:This suggests that adult stem cells in tissues and organs are highly vulnerable to platinum drugs during cancer treatment. Additional studies on localized treatments may help to prevent adverse effects on normal cells.
Stem cell therapy is a promising area of regenerative medicine, offering potential treatments for various life-threatening disorders. Stem cells are classified based on their differentiation potential into totipotent, pluripotent, and multipotent stem cells. Among them, mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their tissue regeneration capabilities and ability to differentiate into multiple cell types. Stem cells are being explored for treating neurodegenerative disorders like Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). These conditions result from progressive neuronal degeneration, leading to irreversible damage. Challenges such as cell survival, immune rejection, tumor formation, and ethical concerns related to embryonic stem cells need to be addressed. Nanotechnology is emerging as a tool for enhancing stem cell therapy, improving targeted delivery and effectiveness. Nanoparticles possess the ability to create microenvironments as substrates, facilitate targeted administration, and enable real-time, precise imaging of stem cells. This review explores the integration of stem cells and nanotechnology as regenerative medicine tool for neurodegenerative disease treatment, analyzing current strategies and therapeutic approaches. Integrating nanotechnology with stem cell therapy may significantly improve targeted delivery and enhance regenerative outcomes for neurodegenerative disorders.
OBJECTIVE:Conditioned medium of umbilical cord mesenchymal cells is a rich environment in various growth factors and cytokines, the use of which causes self-improvement and self-renewal in damaged tissues. METHODS:Therefore, we investigated the effect of Wharton's umbilical cord mesenchymal cells on cytokines, growth factors expression, and skin wound healing in diabetic rats. Rats were divided into two groups of ten. In the treated diabetic group, 1 ml of conditioned medium was used intradermally, and in the diabetic control group, the same amount of physiological serum was used. The tissue samples were evaluated for histological studies. The expression level of inflammatory/anti-inflammatory cytokines and growth factors was investigated using RT-PCR and western blotting analysis. RESULTS:Our results showed that wound healing increased in the diabetic rat group with a pleasant environment compared to the control group. It was also found in molecular studies that the expression of anti-inflammatory cytokines and growth factors was significantly increased in the treated samples compared to the control group. In addition, a significant decrease in TGF-β expression as an important inflammatory cytokine observed compared to the control group. CONCLUSIONS:The use of the conditioned environment of Wharton's jelly mesenchymal cells of the human umbilical cord improves the process of wound healing in terms of tissue and also increases the expression of the critical anti-inflammatory cytokines and growth factors. It can be considered a novel approach in wound healing treatment.
