World journal of stem cells最新文献

This article focused on the recent contribution by Jiang et al, who demonstrated that voluntary exercise can significantly potentiate the effects of induced pluripotent stem cell transplantation in a Parkinson's disease (PD) model through activation of the Wnt1-Lmx1a signaling cascade. Jiang et al's findings highlight the role of exercise as a molecular modulator of neurogenesis and support the development of integrated strategies combining physical activity, stem cell transplantation, and biomaterials to improve outcomes in PD. We highlight exercise as a molecular modulator that fosters a neurogenic milieu, recommend examining additional developmental signals (sonic hedgehog, fibroblast growth factor 8, bone morphogenetic protein), and suggest biomaterial-based strategies to support graft survival and integration. We also stress the need to optimize exercise regimens in relation to transplantation, framing these insights within a translational strategy for advancing regenerative therapies in PD.

Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells. It offers a minimally invasive, abundant, and autologous reservoir for therapeutic applications. Among its cellular components, the stromal vascular fraction (SVF) and adipose-derived stem cells (ASCs) have gained considerable attention due to their potent regenerative and immunomodulatory capacities. SVF is a heterogeneous mixture of cells, whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion. Together, these cell populations (SVF and ASCs) are described as "living drugs", as they are viable and act as dynamic biological agents within the body. Unlike conventional medicines, living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules, including cytokines, growth factors, and extracellular vesicles. These secreted factors can modulate the surrounding microenvironment, enhance tissue repair, and regulate immune responses. Such paracrine mechanisms often play a more significant role than direct cell replacement, making living drugs versatile tools for regenerative medicine. This review provides a comprehensive overview of SVF and ASCs as living drugs. It discusses their cellular composition, mechanisms of action, methods of isolation, and the regenerative biomolecules they secrete. Furthermore, it explores current and emerging clinical applications, challenges, and future innovations.

Fu et al investigated human adipose-derived mesenchymal stem cell exosomes for androgenetic alopecia, identifying a stable set of 232 proteins and proposing the CDC42-Wnt/β-catenin- glycogen synthase kinase 3β signaling axis. These findings support the potential for clinical translation. To further strengthen clinical relevance, we recommend: (1) More comprehensive exosome characterization, including key marker analysis; (2) Reporting both particle count and protein concentration, and establishing dose-response relationships; (3) Direct validation of CDC42's role through knockout or overexpression experiments; (4) Multi-level evaluation of Wnt/β-catenin signaling; (5) Enhanced biochemical validation in animal models; (6) Quantitative analysis of microneedle delivery parameters and retention; and (7) Early development of a streamlined quality control and safety framework. These methodological advancements will help exosome-based therapies better align with emerging regulatory standards and clinical guidelines. By addressing these aspects, future research can facilitate the safe, effective, and reproducible application of exosome-based treatments in clinical practice.

Background: Pathological calcification is a common feature of many diseases. Calcifying nanoparticles (CNPs) are considered potential inducers of this abnormal calcification, but their specific effects on bone marrow mesenchymal stem cells (BMSCs) remain unclear. BMSCs are key cells in bone formation and repair, and their aberrant apoptosis and calcification are closely related to disease progression.

Aim: To explore whether CNPs can induce apoptosis and calcification in BMSCs and analyzed the relationship between these processes. The differential effects of CNPs and nanoscale hydroxyapatites (nHAPs) in inducing apoptosis and calcification in BMSCs were also compared.

Methods: CNPs obtained in the early stage were identified by electron microscopy and particle size analysis. BMSCs were cultured with various treatments, including different concentrations of nHAPs, CNPs [2 McFarland (MCF) turbidity, 4 MCF, 6 MCF], and a transforming growth factor (TGF)-β inhibitor (SB431542) for 72 hours. The isolated CNPs exhibited the expected sizes and shapes.

Results: Exposure to CNPs and nHAPs suppressed cell proliferation and promoted apoptosis in a concentration-dependent manner, with CNPs exhibiting significantly stronger effects. Alizarin Red staining indicated an increase in calcium deposition with exposure to increasing concentrations of nHAPs and CNPs. Quantitative reverse-transcription polymerase chain reaction results indicated that medium concentrations of nHAPs and CNPs significantly enhanced the expression of pro-apoptotic and pro-calcification markers, whereas the expression of anti-apoptotic Bcl-2 was reduced compared with untreated controls. Western blotting results showed that medium concentrations of CNPs and nHAPs increased the expression of osteopontin, bone morphogenetic protein-2, TGF-β/Smad, Bax, and caspase-3 and decreased Bcl-2 expression compared with controls.

Conclusion: CNPs and nHAPs induced apoptosis and calcification in BMSCs, with CNPs being the most potent. Additionally, the TGF-β inhibitor SB431542 significantly reduced the occurrence of apoptosis and calcification. A correlation was found between apoptosis and calcification, which is likely mediated through the TGF-β/Smad signaling pathway.

Acute respiratory distress syndrome (ARDS) remains without effective targeted reparative therapies and continues to carry a high mortality rate. Here, we comment on a recent study by Zhang et al, who identify a CD146+ subpopulation of mesenchymal stromal cells (MSCs) with superior reparative function in lipopolysaccharide-induced ARDS in mice. Compared with CD146- MSCs, CD146+ MSCs secreted higher levels of reparative paracrine mediators, including hepatocyte growth factor, vascular endothelial growth factor, prostaglandin E2 (PGE2), and angiopoietin 1, better preserved endothelial junctional proteins (VE-cadherin, zonula occludens-1), and more effectively modulated T cell and macrophage phenotypes. Mechanistic studies link these effects to a nuclear factor kappa B (NF-κB)/cyclooxygenase-2/PGE2 signaling axis, as pharmacologic blockade of NF-κB (caffeic acid phenethyl ester) abrogated the benefits. We place these results in the context of MSC heterogeneity research, highlight strengths (mechanistic depth, in vivo validation) and limitations (single animal model, reliance on cell lines rather than primary human cells), and propose next steps: Testing efficacy across diverse ARDS etiologies (viral, aspiration), validating effects in primary human alveolar and endothelial cells, delineating the CD146/NF-κB cascade, developing potency biomarkers (e.g., PGE2), and performing rigorous safety profiling. Strategies to enrich or prime MSCs for CD146-associated NF-κB/cyclooxygenase-2/PGE2 program activity may provide a practical route to higher potency.

One of the most prevalent long-term effects of diabetes is diabetic kidney disease (DKD), which is linked to problems with the metabolism of amino acids, fats, and carbohydrates. The fundamental pathogenic mechanisms of DKD cannot be adequately treated by current clinical medicines; they can only slow the illness's progression to end-stage renal disease. We will concentrate on integrating human umbilical cord mesenchymal stem cell (hUC-MSC)-related mechanisms and potential applications into the therapy of DKD, as this work shows that hUC-MSCs can be used to treat metabolic liver obesity associated with diabetes. Future studies on the connection between hUC-MSCs and related illnesses ought to be promoted.

Hepatic fibrosis is a pathological process characterized by an imbalance between the deposition and degradation of extracellular matrix components. This process is initiated by chronic liver injuries resulting from viral infections, alcoholic liver disease, non-alcoholic fatty liver disease, and autoimmune-mediated hepatic damage. If left untreated, hepatic fibrosis can progress to life-threatening conditions such as cirrhosis and hepatocellular carcinoma. Central to the development of fibrosis is the transdifferentiation of quiescent hepatic stellate cells (HSCs) into proliferative and fibrogenic myofibroblast-like activated HSCs (aHSCs), which play a crucial role in extracellular matrix accumulation and fibrotic tissue formation. Beyond resmetirom, a recently Food and Drug Administration-approved medication for liver fibrosis and nonalcoholic steatohepatitis, there are currently no other established pharmacological treatments available to slow down the progression of these conditions. Moreover, activation of HSCs and formation of hepatic fibrosis have been considered irreversible. Recent studies reported transforming growth factor beta as one of the key regulators of HSCs activation and pathogenesis of hepatic fibrosis. It has been also reported that the features of aHSCs can be reversed to those of quiescent HSCs by modulating transforming growth factor beta mediated pathways. The potential of extracellular vesicles (EVs) as cell free therapeutics to treat hepatic fibrosis has been suggested earlier. However, detailed knowledge of the mechanisms involved in the alleviation of hepatic fibrosis using EVs from mesenchymal stem cells is still lacking. Hence, this review aims to describe the pathogenesis of hepatic fibrosis from the cellular and molecular point of views and shed light on the potential of EVs from mesenchymal stem cells in reversing the properties of aHSCs to their quiescent state.

Background: Mesenchymal stem cell (MSC) extracellular vesicles, particularly exosomes (Exos), are gaining recognition as promising therapeutic tools for cancer due to their capacity to modulate tumor cell biology. Induced pluripotent stem cell-derived MSCs (iMSCs) revealed therapeutic characteristics compared with conventional MSCs due to their proliferative capacity and enhanced differentiation potential.

Aim: To study the impact of Exos derived from iMSCs (iMSC-Exos) and bone marrow MSCs (BMSC-Exos) on PANC1 and MDA-MB-231 cancer cells.

Methods: The iMSCs and BMSCs were characterized based on the International Society for Cellular Therapy (2006) criteria by verifying the expression of MSC-specific markers and their differentiation potential. Exos were isolated from 48-hour conditioned media using sequential ultracentrifugation and characterized based on size, morphology, and expression of surface markers including CD9, CD81, and CD63. PANC1 and MDA-MB-231 cells were treated with the isolated Exos, and their effects on cell proliferation, apoptosis, senescence, and invasion were assessed.

Results: In PANC1 cells iMSC-Exos sustained antiproliferative activity for 48 hours (35% reduction, P < 0.01) while BMSC-Exos had a transient effect. In MDA-MB-231 cells, both Exos lowered proliferation significantly after 48 hours (~28% and ~22% reduction, P < 0.05). Notably, these antiproliferative effects were not associated with apoptosis, but an increase in senescence-like tumor cells was identified as the primary response with iMSC-Exos inducing approximately 2.3-fold higher number of senescence-associated β-galactosidase-positive cells compared with BMSC-Exos across both cancer cell lines. Tumor cell invasion was markedly inhibited in PANC1 and MDA-MB-231 cells in response to iMSC-Exos (~60% and ~45% reduction, respectively, P < 0.001), and only in PANC1 cells in response to BMSC-Exos.

Conclusion: iMSC-Exos effectively inhibited tumor proliferation and invasion via a senescence-like mechanism. These results indicated that iMSC-Exos could serve as a cell-free cancer therapy and merit further animal model evaluation.

The oral microenvironment plays a pivotal role in determining stem cell fate, driving both regeneration and pathological transformation. Emerging evidence suggests that post-translational modifications (PTMs) play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells. These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma (OSCC). At the pathway level, PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase (p38/c-Jun N-terminal kinase) → runt-related transcription factor 2 in regeneration, whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin, and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition. This review expounds on recent advances in PTM-mediated regulatory mechanisms in dental-derived mesenchymal stem cells, outlines their functional implications in inflammatory and tumor microenvironments, and discusses translational strategies-including localized, time-staged PTM modulation for regeneration and pathway-anchored combinations for OSCC-for regenerative medicine and targeted cancer therapies. Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.

Background: Stem cell therapy has been recognized as a promising strategy for enhancing cardiac function after myocardial infarction. Nonetheless, its clinical benefits are frequently limited by the poor survival and differentiation rates of the transplanted cells.

Aim: To clarify the role of hypoxia-inducible factor-1α (HIF-1α)/β-catenin in survival and angiogenesis of peripheral blood mesenchymal stem cells (PBMSCs).

Methods: PBMSCs were isolated from rat abdominal aorta blood and characterized by multipotent differentiation assays. Cells were cultured under hypoxic conditions, followed by either overexpression or silencing of HIF-1α/β-catenin. Proliferative capacity was evaluated via colony formation assays, while cellular senescence was assessed using β-galactosidase staining. The protein and/or mRNA expressions of HIF-1α, β-catenin, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), survivin, Bcl2, Bax, cleaved caspase 3 were detected via western blotting and/or quantitative real-time polymerase chain reaction. PBMSCs co-expressing elevated HIF-1α and β-catenin levels were transplanted into infarcted myocardial tissue to evaluate their therapeutic potential in vivo.

Results: HIF-1α or β-catenin overexpression enhanced self-renewal and inhibit apoptosis of PBMSCs by up-regulating Bcl2 and survivin, down-regulating Bax and cleaved-caspase 3. Besides, HIF-1α or β-catenin overexpression elevated angiogenesis via increasing bFGF and VEGF expressions. Silence of HIF-1α or β-catenin had opposite effect. Upregulation of HIF-1α increased β-catenin expression, whereas modifications in β-catenin did not influence HIF-1α expression. Chromatin immunoprecipitation assay verified that HIF-1α directly modulates β-catenin transcription. In vivo, HIF-1α overexpression significantly improved the retention of transplanted PBMSCs in infarcted myocardium and enhanced myocardial repair. Functional analysis further confirmed that HIF-1α operated through β-catenin, which directly modulated the expression of bFGF, VEGF, survivin, Bcl2, Bax and cleaved caspase 3, thereby coordinating the anti-apoptotic and pro-angiogenic functions of transplanted PBMSCs.

Conclusion: This study highlights the modulatory function of HIF-1α on PBMSCs via β-catenin-driven anti-apoptotic and angiogenic signaling cascade under hypoxia environment, offering a promising strategy for improving the therapeutic effectiveness PBMSCs-based transplantation after myocardial infarction.