American journal of stem cells最新文献

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.

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.

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.

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.

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.

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.

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.

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.

Development and maintenance of the nervous system are governed by a scheduled cell death mechanism known as apoptosis. Very much how neurons survive and function depends on the degree of death in differentiating pseudo-neuronal cells produced from neural stem cells. Different inducers can affect the degree of death in these cells: hormones, medicines, growth factors, and others. Developing inventive therapies for neurodegenerative illnesses depends on a knowledge of how these inducers impact mortality in differentiated pseudo-neuronal cells. Using flow cytometry, Western blotting, and fluorescence microscopy among other techniques, the degree of death in many pseudo-neuronal cells is evaluated. Flow cytometry generates dead cell counts from measurements of cell size, granularity, and DNA content. Whereas fluorescence microscopy visualizes dead cells using fluorescent dyes or antibodies, Western blotting detects caspases and Bcl-2 family proteins. This review attempts to offer a thorough investigation of present studies on death in differentiated pseudo-neuronal cells produced from neural stem cells under the effect of different inducers. Through investigating how these inducers influence death, the review aims to provide information that might direct the next studies and support treatment plans for neurodegenerative diseases. With an eye toward inducers like retinoic acid, selegiline, cytokines, valproic acid, and small compounds, we examined research to evaluate death rates. The findings offer important new perspectives on the molecular processes guiding death in these cells. There is still a complete lack of understanding of how different factors affect the molecular processes that lead to death, so understanding these processes can contribute to new therapeutic approaches to treat neurodegenerative diseases.

Pediatric acquired severe aplastic anemia (SAA), a prevalent non-malignant hematological disorder, presents significant therapeutic challenges and carries considerable risks. Despite substantial progress in immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years, the protracted treatment duration, substantial costs, and significant disparities in long-term survival outcomes among patients remain problematic. Identifying predictors of treatment response before therapy initiation is crucial for optimal clinical decision-making and complication prevention. Recent studies has pinpointed predictive factors for IST and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) efficacy in SAA, fostering the development and utilization of transplantation-based scoring systems for prognosis evaluation. This review summarizes advancements in treating pediatric SAA and discusses key elements that influence the outcomes of IST and haplo-HSCT, aiming to support clinical decision-making in diverse clinical scenarios.