World journal of stem cells最新文献

Background: Mesenchymal stem cells (MSCs) are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation. The tissue source of MSCs has gained attention for its role in influencing their function, accessibility, and readiness for clinical use.

Aim: To identify the most suitable adipose source for MSC isolation and expansion for further applications.

Methods: We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method. The MSCs were examined for their expansion using population doubling time, differentiation capacity using multilineage differentiation induction, surface markers using flow cytometry, and stability of chromosomes using the karyotyping method. Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.

Results: MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2. All adipose-derived MSCs (AD-MSCs) exhibited the typical elongated, spindle-shaped morphology and comparable proliferation rate. They expressed positive surface markers [cluster of differentiation 73 (CD73): > 97%, CD90: > 98%, and CD105: > 95%], and negative markers (< 1%). All MSCs expressed similar levels of stemness genes (octamer-binding transcription factor 4, SRY-box 2, Krüppel-like factor, and MYC), colony-forming, and trilineage differentiation potential. Karyotyping analysis revealed normal chromosomal patterns in all samples, except one sample exhibiting a polymorphism (1qh+). Furthermore, the growth factors and cytokines of hepatocyte growth factor, vascular endothelial growth factor A, interleukin 6 (IL-6), and IL-8 were detected in all AD-MSC conditioned media; but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs, respectively.

Conclusion: These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences, which are suitable for further expansion and various clinical applications.

A recently published prospective study marks a breakthrough for congenital olfactory disorders in children. The study provides the first long-term, three-year follow-up data, robustly demonstrating the durable efficacy and safety of autologous nasal epithelial stem cell transplantation. This work reveals immense therapeutic potential for a condition traditionally considered untreatable. However, this milestone achievement also presents new challenges. To translate this pioneering therapy from a single-center success to a global standard, multicenter, controlled clinical trials must be initiated immediately. Only through rigorous validation can we ensure its widespread adoption and ultimately bring hope to millions of children worldwide.

Background: Breast cancer is one of the most prevalent malignancies affecting women worldwide, with approximately 2.3 million new cases diagnosed annually. Breast cancer stem cells (BCSCs) play pivotal roles in tumor initiation, progression, metastasis, therapeutic resistance, and disease recurrence. Cancer stem cells possess self-renewal capacity, multipotent differentiation potential, and enhanced tumorigenic activity, but their molecular characteristics and regulatory mechanisms require further investigation.

Aim: To comprehensively characterize the molecular features of BCSCs through multi-omics approaches, construct a prognostic prediction model based on stem cell-related genes, reveal cell-cell communication networks within the tumor microenvironment, and provide theoretical foundation for personalized treatment strategies.

Methods: Flow cytometry was employed to detect the expression of BCSC surface markers (CD34, CD45, CD29, CD90, CD105). Transcriptomic analysis was performed to identify differentially expressed genes. Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model. Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns. Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.

Results: Flow cytometric analysis revealed the highest expression of CD105 (96.30%), followed by CD90 (68.43%) and CD34 (62.64%), while CD29 showed lower expression (7.16%) and CD45 exhibited the lowest expression (1.19%). Transcriptomic analysis identified 3837 significantly differentially expressed genes (1478 upregulated and 2359 downregulated). Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes, and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups (P < 0.001). Single-cell analysis revealed tumor cellular heterogeneity, and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes. MED18 gene showed significantly higher expression in malignant tissues (P < 0.001) and occupied a central position in cell-cell communication networks, exhibiting significant correlations with tumor cells, macrophages, fibroblasts, and endothelial cells.

Conclusion: This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches, identified reliable surface markers and key regulatory genes, and constructed a prognostic prediction model with clinical application value.

Background: The incidence of diabetic atherosclerosis (DMA) is increasing worldwide, but its pathogenesis remains incompletely understood. In addition to cardiovascular complications, bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.

Aim: To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles (hAFSC-EVs) on the recovery of bladder dysfunction in DMA rats.

Methods: Eighty rats were divided into normal control, streptozotocin-induced diabetic rats, diabetic rats subjected to arterial balloon endothelial injury of common iliac artery (DMA), and DMA rats treated with hAFSC-EVs (DMA + hAFSC-EVs). At 4 weeks and 12 weeks after DMA induction, levels of blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment (HOMA)-insulin resistance, and HOMA-β were measured. Cystometry, common iliac artery wall thickness, and bladder tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β1, Smad3, connective tissue growth factor (CTGF) and fibronectin were also evaluated.

Results: Bladder weight and blood glucose, triglyceride, HOMA-insulin resistance, common iliac artery intima thickness, voided volume, intercontraction interval, bladder capacity, and mRNA expression of TNF-α, IL-6, TGF-β1, Smad3, CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction, while the HOMA-β level decreased at 4 weeks and 12 weeks, and the high-density lipoprotein cholesterol level decreased at 12 weeks. hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose, thickness of common iliac arterial intima, voided volume, intercontraction interval and bladder capacity at 4 weeks. The mRNA expression of TNF-α, TGF-β1, and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks, while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.

Conclusion: hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction, which is associated with lowered blood glucose levels, reduced arterial wall thickness, and decreased TNF-α, IL-6, TGF-β1, Smad3, and CTGF expression.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options. Notably, Zhang et al demonstrated that CD146+ mesenchymal stromal cells (MSCs) exhibited greater therapeutic efficacy than CD146- MSCs. These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors. We concur that MSCs hold significant promise for ARDS treatment; however, the heterogeneity of cell products is a translational barrier. Phenotype-aware strategies, such as CD146 enrichment, standardized potency assays, and extracellular vesicle profiling, are essential for improving the consistency of these studies. Furthermore, advanced preclinical models, such as lung-on-a-chip systems, may provide more predictive insights into the therapeutic mechanisms. This article underscores the importance of CD146+ MSCs in ARDS, emphasizes the need for precision in defining cell products, and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.

Background: Cancer stem cells (CSCs) drive recurrence and therapeutic resistance in triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype. Intratumoral hypoxia, a common feature of solid tumors, promotes CSCs enrichment, yet the mechanisms sustaining CSCs stemness remain poorly understood. Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasia mutated (ATM) kinase (oxidized ATM, p-ATM) independently of DNA breaks.

Aim: To investigate the role of hypoxia-induced oxidized ATM in sustaining TNBC-CSC stemness through c-Myc-mediated regulation of one-carbon metabolism.

Methods: Hs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia. CSC stemness was assessed by mammosphere assays and flow cytometry. ATM activity was assessed by pharmacological inhibition (Ku60019) and short hairpin RNA knockdown. c-Myc binding to serine hydroxymethyltransferase 2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) promoters was analyzed by dual-luciferase reporter assays and chromatin immunoprecipitation. NADPH/NADP+ ratios were quantified, and metabolic reprogramming was profiled by liquid chromatography-tandem mass spectrometry metabolomics.

Results: Hypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells, as reflected by higher numbers of mammospheres (Hs578T: 214 ± 18; MDA-MB-231: 198 ± 16; both P < 0.01) and larger mean diameters (P < 0.01). Hypoxia also elevated CD44+/CD24- cell proportions and stemness gene expression (P < 0.01). Oxidized ATM was activated under hypoxia without γH2AX induction, confirming DNA damage independence. ATM inhibition reduced mammosphere growth and suppressed c-Myc, SHMT2, and MTHFD2. Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2 promoters, while mutation of the binding sites abolished promoter activity. NADPH/NADP+ ratios were significantly elevated under hypoxia but reduced following ATM inhibition (P < 0.05). Metabolomics revealed enrichment of serine/glycine one-carbon pathways.

Conclusion: Hypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation of MTHFD2 and SHMT2, linking hypoxia, redox signaling, and one-carbon metabolism. These findings suggest a potential therapeutic axis that could be exploited for TNBC treatment.

A recent preclinical study reported that Wumei Pills (WMP) and Lactobacillus reuteri (L. reuteri) mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell (ISC)-mediated repair via Wnt/β-catenin signaling. The mechanistic interpretation rests largely on systemic inflammation readouts, correlative microbiota changes, and immunohistochemistry of pathway markers. From a clinical standpoint, chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions, treatment delays, and infection risk; current care is largely supportive and does not directly restore ISC-mediated repair. This unmet need motivates rigorous appraisal of the proposed "WMP → L. reuteri → ISC/Wnt" axis. To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed "WMP → L. reuteri → ISC/Wnt" pathway. This letter critically appraises the study's design, endpoints, and analyses against current best practices in mucositis biology, microbiome causality testing, Wnt/β-catenin pathway validation, and preclinical statistics, and synthesizes concrete, literature-grounded remedies. Six issues with potential impact on interpretation were identified: (1) Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation, with limited tissue-level indices (e.g., myeloperoxidase, interleukin-1β, immune-cell infiltration); (2) Absence of necessity/sufficiency tests to verify microbiota mediation (e.g., L. reuteri depletion, WMP-donor fecal microbiota transplantation, probiotic add-back); (3) Pathway evidence tiering - Wnt/β-catenin activation not confirmed by β-catenin nuclear translocation or downstream targets (Axin2, c-Myc, cyclin D1), and Lgr5 quantification/specificity insufficient; (4) Statistical design under-specified (power justification, blinded assessment, control of multiple comparisons) and potential cage effects unmodeled; (5) Limited dose-response and safety profiling for WMP/L. reuteri; and (6) Constrained generalizability (single sex/strain/age, lack of ABX-only controls, single time-point). The reported benefits of WMP and L. reuteri in chemotherapy-induced mucositis are promising, but stronger causal and analytical foundations are needed. Incorporating tissue-level inflammation readouts, microbiota loss-/gain-of-function designs, definitive Wnt/β-catenin activation assays, rigorous statistical practices (including mixed-effects models for cage clustering and multiplicity control), dose-response/safety evaluation, and broader experimental scope (sex/age/strain, ABX-only controls, time-course) will yield more robust and translationally relevant conclusions.

Regenerative medicine is a promising therapeutic avenue for previously incurable diseases. As the risk of chronic and degenerative diseases significantly increases with age, the elderly population represents a major cohort for stem cell-based therapies. However, the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor. Therefore, the efficacy of autologous stem cell therapy is significantly compromised in older patients. To overcome these limitations, alternative strategies have been used to restore the age- and disease-depleted function of stem cells. These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use. This article explores the effect of donor age and health status on the regenerative potential of stem cells. It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly. A comprehensive insight into the potential strategies to address the "age" and "disease" compromised regenerative potential of autologous stem cells is also presented. The information provided here serves as a valuable resource for physicians and patients for optimization of stem cell-based autologous therapy for aged patients.

We read with the great interest the study by Ababneh et al in which induced mesenchymal stem cell-derived exosomes were shown to exhibit a stronger and more sustained anti-proliferative effect by inducing a senescence-like state without apoptosis. The results obtained by the authors highlight the features of the effects of senescent drift induction in surrounding tissues. In the light of these findings, the role of the properties of extracellular matrix and cellular glycocalyx in responses of human tumors to therapy remain uninvestigated. These extracellular barriers appear to be significant obstacles to effective cancer therapy, especially in relation to the use of unique properties of tumor microenvironment for the immunotherapy-resistant cancer treatment.