搜索结果：Stem cell reviews and reports

A comprehensive understanding of how diverse adult stem cell populations function in harmony is crucial for maintaining homeostasis and ensuring the normal functioning of body tissues. Two types of stem cells in adult tissues have attracted attention, including very small embryonic-like stem cells (VSELs) and multi-lineage differentiating stress-enduring cells (MUSE), reported for the first time in 2006 and 2010, respectively. VSELs are pluripotent stem cells developmentally linked to the primordial germ cells, while MUSE cells, initially described as multipotent, are now being defined as having pluripotent characteristics and further differentiate into MSCs. VSELs are the most primitive, virtually immortal and pluripotent stem cells that survive lifelong in all tissues in small numbers and undergo asymmetrical divisions to give rise to tissue-specific progenitors of different sizes and fates. VSELs are 5-7 μm in size, spherical in shape, with a cell surface profile of LIN-CD133 + CD45- while MUSE cells are 10-15 μm in size, with abundant cytoplasm, horseshoe/bean-shaped nuclei, cytoplasmic OCT-4 and are CD45+, like hematopoietic stem cells. In the mouse uterus, VSELs undergo cyclic changes in response to circulatory hormones, regenerate both the epithelial and stromal compartments in an atrophied uterus (upon bilateral ovariectomy, in the absence of macrophages) and also upon chronic injury. Exposure to endocrine-disrupting chemicals disrupts the functions of VSELs and results in various pathologies, including endometrial cancer. The crucial role of dysfunctional VSELs resulting in cancer initiation, progression, metastasis and recurrence was recently discussed. On the other hand, multiple clinical trials have reported the potential of MUSE cells for ensuring regeneration upon transplantation. VSELs regenerate damaged and diseased tissues when a healthy paracrine support is provided by the transplanted MUSE cells/MSCs; however, remain elusive due to their small size and scarce nature. In summary, the view that MUSE cells phagocytose damaged cells and subsequently differentiate into the same cell type is fundamentally challenged and requires careful re-evaluation.

The present manuscript provides a comprehensive overview of neural stem cell (NSC)-derived extracellular vesicles (NSC-EVs( as a cell-free approach to treating central nervous system (CNS) disorders. The study noted that NSCs are regenerative and neuroprotective, but direct transplantation is limited by short survival, immunological rejection, and tumorigenic risk. However, NSC-EVs-nano-sized vesicles loaded with proteins, lipids, and RNAs-can replicate many of their parent cells' benefits without safety or ethical issues. NSC-EVs are the source of numerous biologically active molecular cargoes. Encompassing (BDNF, GDNF, VEGF), signaling lipids, and microRNAs (miR-124, miR-21, miR-146a, miR-219) that are essential in modulating and regulating key processes involved in the induction of neurogenesis, promoting angiogenesis, reducing inflammatory milieu, and improving neuronal survival. In preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI), these vesicles reduce oxidative stress, suppress apoptosis, modulate microglia activation, enhance synaptic plasticity, and promote remyelination. Numerous translational obstacles remain, including heterogeneous EV isolation techniques, limited scalability of clinical-grade manufacturing, and inconsistent elucidation of long-term safety and biodistribution. This review discusses the therapeutic potential of NSC-EVs for neurological and neurodegenerative diseases. Additionally, leveraging the powerful, precise analytical capabilities of Artificial Intelligence (AI) with recent multi-omics data from NSC-EVs will improve the characterization and predictability of therapeutic efficacy. Combining the therapeutic potential of stem cells with the non-invasive, practical, and safe cell-free biologic is expected to transform regenerative neuroscience. A promising aim that requires establishing a multidisciplinary approach among neuroscientists, bioengineers, and clinicians to standardize the isolation process, validate the underlying mechanistic information, and test their therapeutic potential at the clinical level. The present review concludes that NSC-EVs are a promising research topic in regenerative neurotherapy, offering a potential therapeutic strategy for incurable neurological and neurodegenerative diseases.

Cell fate determination and terminal differentiation are shaped by intrinsic molecular programs that coordinate lineage-specific gene expression. In mesenchymal stem cells (MSCs), variability in osteogenic efficiency among distinct tissue sources remains poorly understood and cannot be fully explained by differentiation conditions alone. Increasing evidence indicates that post-transcriptional regulatory mechanisms, particularly those mediated by microRNAs (miRNAs), are closely associated with differentiation outcomes. Here, we investigated whether intrinsic miRNA expression landscapes are associated with lineage-associated differences in late-stage mineralization, in the context of potential donor-related variability of human MSCs. Dental pulp stem cells (DPSCs) and processed lipoaspirate (PLA)-derived MSCs were cultured under identical osteogenic induction conditions and analyzed longitudinally throughout differentiation. Both cell populations fulfilled established mesenchymal phenotypic criteria and successfully initiated osteogenic commitment. However, DPSCs exhibited significantly enhanced extracellular matrix mineralization at mid-to-late stages of differentiation, suggesting divergence at later stages of extracellular matrix mineralization rather than at early lineage commitment. Temporal small RNA sequencing performed at days 0, 7, 14, and 21 revealed progressive remodeling of miRNA expression in both MSC sources. Direct comparison at the mature osteoblast stage identified a discrete set of ten miRNAs differentially expressed between DPSCs and PLA-derived cells. DPSCs displayed reduced expression of several miRNAs previously associated with inhibitory roles in osteogenic pathways. Network-based analyses indicated convergence of these miRNAs on gene programs involved in skeletal development and extracellular matrix organization. Targeted validation confirmed decreased expression of miR-10a-5p and miR-196a-5p, accompanied by increased expression of osteogenesis-associated genes, including BMP1 and MMP16, in DPSCs. Collectively, these findings show that lineage-specific miRNA expression patterns are associated with distinct osteogenic maturation trajectories in human MSCs. This work identifies an intrinsic post-transcriptional signature through which cellular origin may influence terminal differentiation outcomes and suggests that such miRNA profiles may serve as informative molecular biomarkers in the future for the selection and characterization of mesenchymal stem cells intended for human bone tissue engineering applications. The online version contains supplementary material available at 10.1007/s12015-026-11107-7.

Cell therapy for neurodegenerative diseases (NDs) is considered a promising strategy to halt disease progression. Currently, most clinically applied cells are derived from two-dimensional (2D) cultures. However, 2D-cultured mesenchymal stem cells (MSCs) are prone to aging and functional deterioration after multiple passages, and the availability of neural precursor cells for cell replacement therapy remains limited. In contrast, three-dimensional (3D) cell cultures have garnered significant attention due to their unique 3D spatial interactions. The unique spatial architecture of 3D culture not only enhances cell-cell and cell-extracellular matrix (ECM) interactions in MSC spheroids, thereby preserving MSCs properties, but also facilitates developmental processes of brain organoids derived from pluripotent stem cells, including embryogenesis, morphogenesis, and organogenesis. This review highlights the therapeutic ability of 3D-cultured MSC spheroids and brain organoids for NDs and summarizes advanced engineering platforms for their production. Future research should integrate the strengths of both technologies by establishing standardized quality control systems and scalable production processes to harness the microenvironmental modulation capacity of MSC spheroids and the precise cell replacement ability of brain organoids, ultimately advancing personalized therapies for NDs.

Arthritis, encompassing degenerative disorders such as osteoarthritis (OA) and autoimmune diseases like rheumatoid arthritis (RA), remains a leading cause of chronic pain, disability, and socioeconomic burden worldwide. Conventional pharmacological and surgical therapies primarily offer symptomatic relief without addressing the underlying degeneration of cartilage and bone. Recent advances in regenerative medicine have introduced promising biological strategies, particularly mesenchymal stem cells, exosomes, and bioengineered tissue scaffolds, for functional joint restoration. MSCs exhibit remarkable differentiation potential, along with immunomodulatory and paracrine effects that support cartilage repair and immune homeostasis. MSC-derived exosomes replicate many of these therapeutic functions through their bioactive cargo of proteins, lipids, and microRNAs, offering a safer and more controllable cell-free alternative. Meanwhile, bioengineered scaffolds composed of natural or synthetic polymers provide essential structural and biochemical cues for tissue regeneration, especially when integrated with stem cells or exosomes. Despite encouraging preclinical and early clinical outcomes, challenges remain concerning safety, standardization, scalability, and regulatory approval. The integration of emerging technologies such as nanotechnology, artificial intelligence, and gene editing may further enhance regenerative outcomes and enable personalized arthritis therapies. Collectively, these convergent innovations represent a paradigm shift from symptomatic management toward true biological repair, positioning regenerative and stem cell-based therapies at the forefront of next-generation arthritis treatment.

Mitochondrial protein import and transporter systems play essential roles in maintaining metabolic competence and proteostasis in stem cells. However, the transcriptional architecture of mitochondrial translocase (TOM/TIM) complexes and transporter genes in human spermatogonial stem cells (SSCs) remains poorly defined. We performed an integrative analysis combining bulk microarray profiling of human SSC-enriched populations (n=3 biological replicates per group) with complementary single-cell RNA-sequencing (scRNA-seq) datasets. Differential expression (limma; |log&#x2082;FC| &#x2265; 2, adj. P&#x2009;<&#x2009;0.05), co-expression network construction (WGCNA), protein-protein interaction mapping (STRING/cytoHubba), and miRNA-mRNA regulatory inference were used to identify key mitochondrial transporter nodes. Validation of hub-gene expression patterns was performed using an independent scRNA-seq dataset. Cell-type identity of SSC-enriched cultures was confirmed by immunocytochemistry for established SSC markers. Integrated multi-omics analyses revealed a coordinated enrichment of mitochondrial transporter genes in SSCs, including upregulation of TOMM and TIMM family members and selected ATPase and SLC transporters relative to fibroblasts. Hub genes (TOMM22, TIMM17A, ATP6V1A, SLC25A3) showed high network centrality and were consistently enriched in undifferentiated SSC clusters across multiple scRNA-seq datasets. miRNA-mRNA interaction modeling identified several SSC-expressed miRNAs (e.g., hsa-miR-4732-3p, hsa-miR-6503-3p) as potential post-transcriptional regulators of mitochondrial transporter networks. Human SSCs exhibit a distinctive mitochondrial transporter gene program characterized by enhanced expression of protein-import machinery and metabolic transport components. These findings provide a comprehensive molecular framework for understanding mitochondrial regulation in SSCs and establish new candidate targets for probing germline metabolism and stem-cell maintenance.

This systematic review aimed to synthesize current evidence on the regulatory role of microRNAs (miRNAs) in the viability, proliferation, osteo-odontogenic differentiation potential and/or inflammation of periodontal ligament stem cells (PDLSCs) and stem cells from the apical papilla (SCAPs), with a focus on their potential in periodontal and endodontic regeneration. A comprehensive search across Medline, Scopus, Embase, Web of Science, and SciELO databases up to December 2025 identified original in vitro studies assessing miRNA overexpression or knockdown in PDLSCs or SCAPs. 39 studies met the eligibility criteria and underwent structured data extraction, qualitative synthesis and quality appraisal using a tailored risk-of-bias tool (miRoB-DSC). The findings demonstrate that specific miRNAs act as key regulators of PDLSCs and SCAPs viability, proliferation, osteo-odontogenic differentiation, and inflammatory responses. Comparisons with previous reviews on DPSCs and PDLSCs suggest both shared and niche-specific regulatory networks. Various signaling pathways have been majorly implicated with miRNA regulation, including RUNX2, Smad/TGF&#x3b2;, NOTCH, NF-&#x3ba;B, Wnt/&#x3b2;-catenin and MAPK. The majority of the assessed studies fulfilled more than 80% of the applicable items from the miRoB-DSC tool. Collectively, these results highlight miRNAs as central modulators of PDLSC and SCAP biology, with potential applications as therapeutic targets or biomarkers in regenerative dentistry. However, heterogeneity in experimental designs, limited evaluation under disease-relevant conditions, and the reliance on in vitro models highlight the need for standardized protocols and in vivo validation before clinical translation. The online version contains supplementary material available at 10.1007/s12015-026-11088-7.

The family of P2Y purinergic receptors, which are G protein-coupled seven-transmembrane receptors, is activated by various purine and pyrimidine nucleotides, including adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine triphosphate (UTP), uridine diphosphate (UDP), and UDP-glucose.&#xa0;To date, eight P2Y receptors have been&#xa0;identified&#xa0;in humans:&#xa0;P2Y1,&#xa0;P2Y2,&#xa0;P2Y4,&#xa0;P2Y6,&#xa0;P2Y11,&#xa0;P2Y12, P2Y13, and P2Y14, whereas in mice, seven have been identified because P2Y11 is not present. Among these receptors, only P2Y2 and P2Y11 in human cells respond to extracellular ATP (eATP); since P2Y11 is absent in murine cells, the P2Y2 receptor alone responds to the eATP gradient.&#xa0;In our previous work, we established the role of several P2X receptors in the trafficking of hematopoietic stem/progenitor cells (HSPCs) and detected considerable redundancy in responsiveness to eATP. Because the P2Y2 receptor is also activated by eATP and is expressed on murine HSPCs, we investigated its role in eATP-mediated trafficking of these cells. We focused on chemotaxis and pharmacological mobilization of bone marrow (BM) cells into peripheral blood (PB). In this report, we ruled out a role for other P2Y receptors in HSPC trafficking, as ligands such as ADP, UTP, UDP, UDP-glucose, and GTP did not chemoattract clonogenic HSPCs, although they attracted other non-clonogenic BMMNCs. To examine the specific role of P2Y2 in HSPC trafficking, we used the small-molecule inhibitor AR-C118925XX of this receptor. We observed that the migration of human and murine HSPCs in Transwell chambers toward eATP was inhibited after exposure to AR-C118925XX. Furthermore, administration of this inhibitor during pharmacological mobilization of HSPCs in mice challenged with G-CSF or AMD3100 resulted in reduced mobilization compared to control animals. We also observed impaired mobilization of other types of BM-residing stem/progenitor cells, including mesenchymal stromal cells (MSCs), endothelial progenitors (EPCs), and very small embryonic-like stem cells (VSELs). These findings indicate that, along with ionotropic P2X receptors, the P2Y2 receptor contributes to optimal mobilization of bone marrow-residing stem cells, and that eATP is the only promigratory nucleotide among all purinergic signaling ligands for HSPCs. [Image: see text]

Ischemic stroke (IS), also referred to as cerebral ischemia, is a neurological condition accompanied by long term or permanent physical disability. Various molecular mechanisms such as inflammation, oxidative stress, blood brain barrier (BBB) disruption, energy depletion, mitochondrial dysfunction etc., contribute to its pathophysiology and trigger death of neural tissues. Currently, there are limited therapeutic options for its treatment. Although, thrombectomy or thrombolytic drugs are available, but only beneficial for the management of acute phase and do not address the neurodegenerative aspects. Mesenchymal stem cells (MSCs) are predominantly used for regenerative applications due to their self-renewal, immunomodulatory, and neuronal differentiation potential which make them a suitable candidate for neural tissue regeneration at both pre-clinical and clinical levels. MSC derived exosomes and extracellular vesicles (EVs) also provide cell-free therapeutic option that potentially reduce inflammation, restore BBB integrity, and facilitate neural regeneration. The current review summarizes the molecular mechanisms associated with IS pathophysiology and therapeutic mechanisms exhibited by MSCs and their derived products. Furthermore, the review also highlights the clinical trials registered so far to examine the efficacy of MSCs and their derived products to validate the findings and address challenges associated with preclinical studies. A number of clinical trials have reported improvements in motor functions and neurological scores, demonstrating MSC based therapy as safe and effective to treat IS complications. However, there is still a need to fully optimize protocols for MSC source, delivery route, dose, and timing of administration to maximize therapeutic efficacy and ensure safety in future clinical applications.

Percutaneous autologous expanded CD34&#x207a; cell therapy (ProtheraCytes&#xae;) has demonstrated feasibility, manageable safety concerns and a regenerative potential in the EXCELLENT phase I/IIb trial (NCT02669810). Objective of our study was to assess HRQoL over 6 months following ProtheraCytes&#xae; therapy in patients with recent large AMI and left ventricular (LV) dysfunction. EXCELLENT was a multicenter, randomized, open-label, controlled phase I/IIb trial enrolling 77 AMI patients. Participants were randomized 3:1 to standard-of-care (SoC) plus transendocardial ProtheraCytes&#xae; injections or SoC alone. The per-protocol population included 49 subjects. Of those, 31 treated and 12 control patients were analyzable with complete baseline and follow-up 36-Item Short Form Survey (SF-36) data. HRQoL domains and composite scores were analyzed using repeated-measures ANCOVA adjusted for baseline values. At baseline, HRQoL was markedly impaired, consistent with severe LV dysfunction (mean physical functioning score at 63.3, LVEF 35.2%, elevated NT-proBNP). At 6 months, the treated group showed significant and sustained meaningful improvements in physical functioning (+&#x2009;16.6 PF, p&#x2009;=&#x2009;0.0002), vitality (+&#x2009;12.7 VT, p&#x2009;=&#x2009;0.0072), social functioning (+&#x2009;17.9 SF, p&#x2009;=&#x2009;0.0059), and bodily pain (+&#x2009;17.0 BP, p&#x2009;=&#x2009;0.0031). Between months 3 and 6, most HRQoL domains declined in controls but remained stable or improved in treated patients. In conclusion, ProtheraCytes&#xae; therapy was associated with significant HRQoL gains sustained over 6 months, alongside biological improvements. These findings support further evaluation of expanded CD34&#x207a; cell therapy to address the unmet need for durable functional recovery post-AMI.

Breast calcifications are frequent mammographic findings and serve as critical indicators for the early detection of breast cancer. Breast calcifications are formed by a mineralization process considered passive deposits resulting from tissue necrosis, but accumulating evidence suggests that calcifications may instead arise from active stromal remodeling within the tumor microenvironment. Among the diverse stromal components, mesenchymal stem cells are particularly implicated in mediating mineralization processes. Adipose-derived mesenchymal stem cells (ADSCs), abundant in breast tissue and possessing strong osteogenic potential, could therefore play a key role in mineralization process. However, their contribution of ADSCs to malignant calcification formation remains poorly understood. RNA sequencing was performed on malignant and benign calcified breast tissues to identify differentially expressed genes. Candidate genes were validated using public datasets, immunohistochemistry and survival analysis. ADSCs were isolated from patient breast tissue, phenotypically characterized and genetically modified to overexpress SQLE or HGD genes. Osteogenic differentiation was assessed by alkaline phosphatase activity, Alizarin Red S staining, qPCR and Western blot. In vivo effects were evaluated using a breast cancer xenograft model. Transcriptomic profiling, Seahorse mitochondrial stress analysis, JC-1 staining, reactive oxygen species (ROS) quantification, calcium imaging and transmission electron microscopy were used to explore the underlying mechanisms. Transcriptomic screening identified SQLE as a top upregulated gene in malignant calcifications, correlating with poor patient survival. SQLE was highly expressed in stromal cells of malignant lesions. Functional assays showed that the overexpressed SQLE markedly enhanced ADSC osteogenic differentiation and matrix mineralization, with a stronger effect than HGD. In vivo, SQLE-overexpressing ADSCs promoted ectopic calcification within tumors. Mechanistically, the overexpressed SQLE altered the ADSC transcriptome, enriched cancer- and calcium-related pathways, impaired mitochondrial oxidative phosphorylation, reduced mitochondrial membrane potential and ROS levels, and induced mitochondrial calcium accumulation with mineral deposition. The upregulation of PMCA2 and MCU mediated by overexpressed SQLE occurred prior to differentiation, followed by sustained mitochondrial calcium accumulation. This study identifies SQLE as a novel driver of stromal mineralization and malignant breast calcification via mitochondrial dysfunction and calcium dysregulation. These findings challenge the passive necrosis model of calcification, positioning SQLE as both a biomarker for malignant calcifications and a potential therapeutic target for microenvironment-focused breast cancer interventions.

Purinergic signaling plays an important role in hematopoietic stem/progenitor cell (HSPCs) trafficking, and the role of extracellular alarmin adenosine triphosphate (ATP), a major purinergic signaling mediator, is well established. Another alarmin, uridine diphosphate glucose (UDP-glucose), has also been reported to promote HSPCs trafficking after binding to the P2Y14 purinergic receptor. The molecular basis for this phenomenon, however, remains unclear, especially because UDP-glucose alone does not chemoattract HSPCs. To address this question, we hypothesize that UDP-glucose's role in stem cell trafficking may involve promoting the formation of membrane lipid rafts (MLRs) and enhancing intracellular activation of the Nlrp3 inflammasome, which we have previously identified as essential regulators of HSPCs migration. We found that UDP-glucose promotes HSPCs mobilization not only in response to the pro-mobilizing agent G-CSF but also in response to AMD3100. Furthermore, for the first time, we demonstrate that UDP-glucose also promotes homing and engraftment of HSPCs. We also evaluated the biological effects of a newly synthesized UDP-glucose analog, MRS2690. Our studies included HSPCs in vitro and in vivo trafficking assays, immunostaining and confocal analysis to assess MLRs formation on HSPCs, supported by metabolic analyses to identify metabolites involved in MLRs formation.&#xa0;Our data support our hypothesis that activation of the P2Y14 receptor on HSPCs by its ligands positively modulates cell trafficking, primarily by promoting lipid raft formation and Nlrp3 inflammasome activation. Interestingly, one of the components of MLRs upregulated in response to UDP-glucose is sphinganine, which serves as a fundamental building block and intermediate in the de novo biosynthesis of sphingolipids. [Image: see text] The online version contains supplementary material available at 10.1007/s12015-026-11104-w.

Salivary hypofunction and xerostomia are major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy of the head and neck and Sj&#xf6;gren&#x2019;s disease. An increasing number of clinical human studies suggest that mesenchymal stem cell (MSC) therapy can ameliorate symptoms of xerostomia. However, a meta-analysis is yet to summarize the results. The primary outcome of this study was unstimulated salivary flow rate (UWS) after treatment with MSCs. The MEDLINE, EMBASE, and Cochrane databases were searched for eligible studies. Eligible studies were: clinical studies including patients with salivary hypofunction due to either radiotherapy or Sjogren&#x2019;s disease who were subsequently treated with MSCs. A meta-analysis was conducted for the included randomized controlled trials. Secondary outcomes include method of administration, number of MSC used, change in patient reported outcomes, development of drug-specific antibodies, and safety. Eight studies were included describing 5 clinical trials. 230 participants were treated, hereof 126 received MSC treatment. In the meta-analysis, an increase in UWS of 0.06 mL/min (95%CI: -0.05 to 0.17) were found. In a subgroup analysis of radiation induced xerostomia, a significant increase in UWS of 0.03 mL/min (95%CI: 0.01 &#x2013; 0.05) were found. All trials reported improvement in patient reported outcomes. Further, no treatment-related serious adverse events were reported, and few, minor, and temporary adverse events was observed. MSC therapy for xerostomia showed a potential but modest benefit in improving salivary gland function. Further, MSC treatment was found to be safe with minor, temporary adverse events. The online version contains supplementary material available at 10.1007/s12015-026-11105-9.

Induced pluripotent stem cell (iPSC)-derived &#x3b2;-like cells hold great promise for cell replacement therapy in type 1 diabetes. However, the reprogramming process generates iPSC clones with variable differentiation capacity, hindering the selection of optimal cell lines. This study aimed to identify an early-stage transcriptional signature capable of predicting the &#x3b2; cell differentiation potential of donor-matched iPSC clones. Eleven iPSC clones derived from a single donor were differentiated to the definitive endoderm (DE) stage; six were further driven toward pancreatic progenitors (PP) and insulin-producing cells. Differentiation efficiency was evaluated by flow cytometry and qPCR at iPSC, DE, PP, and &#x3b2; cell stages. At the pluripotent stage, expression profiling of 770 genes related to pluripotency and trilineage specification was performed to identify predictive molecular markers. Transcriptomic analysis segregated the clones into two groups (Gr1 and Gr2) with significantly different differentiation outcomes. Gr2 clones exhibited superior DE efficiency (Cxcr4&#x207a;: 90.1&#x2009;&#xb1;&#x2009;5.6% vs. 79.8&#x2009;&#xb1;&#x2009;3.6%; P&#x2009;=&#x2009;0.027) and higher expression of PP markers (Pdx1&#x207a;, Nkx6.1&#x207a;, and double-positive cells; P&#x2009;&#x2264;&#x2009;0.05). At the &#x3b2; cell stage, Gr2 clones showed increased frequencies of Pdx1&#x207a;/Ins&#x207a; and Nkx6.1&#x207a;/Ins&#x207a; cells (P&#x2009;&#x2264;&#x2009;0.05), along with enhanced glucose-stimulated insulin secretion. A set of 73 differentially expressed genes, enriched in pathways related to na&#xef;ve/primed pluripotency, endoderm commitment, and metabolism, was identified. From this, a ten-gene signature validated by qPCR strongly correlated with pancreatic marker expression at all stages. An early gene expression signature at the pluripotent stage predicts the pancreatic endocrine differentiation potential of iPSC clones. This molecular screening approach may enable rapid preselection of high-performing clones, thereby accelerating the development of personalized stem cell&#x2013;based therapies for diabetes.&#xa0; Cellular reprogramming is a fundamental tool in regenerative medicine but often produces iPSC clones with heterogeneous differentiation potential. Identifying the most suitable clones typically requires time-consuming assays and prolonged in vitro testing. This study presents a streamlined transcriptomic approach to predict, at the pluripotent stage, the differentiation efficiency of iPSC clones into pancreatic endoderm and insulin-producing cells, enabling early selection of high-performing lines for the development of diabetes cell therapy. The online version contains supplementary material available at 10.1007/s12015-026-11091-y.

Immunometabolism has emerged as a central regulator of immune responses, linking cellular metabolism to inflammatory signaling and tissue homeostasis. Among tricarboxylic acid (TCA) cycle-derived metabolites, itaconate has gained recognition as an important metabolic feedback regulator promoting inflammatory resolution. Mesenchymal stromal/stem cells (MSCs) are multipotent cells widely recognized for their immunomodulatory and regenerative properties, primarily mediated through paracrine signaling and metabolic adaptation. Increasing evidence indicates that MSC immunoregulatory function is closely associated with metabolic reprogramming involving glycolysis, mitochondrial activity, lipid metabolism, and amino acid pathways. Within this context, itaconate has emerged as a potential metabolic interface linking innate immune activation to MSC function. This narrative review summarizes current evidence supporting both direct and indirect interactions between itaconate signaling and MSC biology. Itaconate and its derivatives influence MSC viability, apoptosis resistance, differentiation potential, and redox balance, while indirectly modulating macrophage polarization and inflammatory microenvironment remodeling through extracellular vesicles and paracrine communication. Despite these advances, critical questions remain regarding endogenous itaconate production by MSCs and its effects on MSC secretome composition and immunoregulatory activity. A deeper understanding of the itaconate-MSC axis may enable metabolic preconditioning strategies aimed at enhancing MSC-based therapies for inflammatory and immune-mediated diseases.

Wound healing is complex, and hard-to-heal (chronic) wounds pose significant treatment challenges, especially in adults. Micrografts (MGs) are emerging as a promising treatment for wounds refractory to conventional approaches. MG involves transplanting a stem cell suspension to the wound to promote healing. Scientific studies on MG are increasing; however, a systematic review is needed for a comprehensive understanding of its efficacy. A systematic review conducted on 30 March 2024 used PubMed, Scopus and Web of Science databases to evaluate skin and dermal MGs in wound healing. PRISMA guidelines were followed and predefined inclusion and exclusion criteria were applied. All authors reviewed the studies and discussed results to ensure consistency in study screening, selection and data extraction. A total of 1251 papers were examined, with 23 eligible for full-text review. After exclusions based on language, reviews, MG size and tissue focus, 15 articles were included in the final review: seven case reports; five case series; two prospective series (one with 70 patients, the other with 30 patients) and a case-control study. The results of the reviewed studies suggest that MGs may promote wound healing, with reported reductions in healing time and improvements in clinical symptoms in hard-to-heal wounds. However, standardisation of treatment protocols and application methods is required. The role of MGs in the treatment of acute wounds remains to be clarified.

Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) are promising therapies across cardiovascular, inflammatory, metabolic, and neurodegenerative diseases. Metabolomics has revealed how MSCs/EVs reshape host metabolism, but current studies remain fragmented, small, and largely descriptive. Synthesizing evidence across disease models, we identify conserved metabolic checkpoints, succinate and &#x3b1;-ketoglutarate in the TCA cycle, acylcarnitines in fatty acid &#x3b2;-oxidation, and glutathione in redox balance, as recurrent targets linked to therapeutic benefit. Distinct signatures, including polyamine metabolism, bile acid&#x2013;FXR/TGR5 signaling, and neurotransmitter regulation, provide disease-specific insights. Yet, most studies lack validation and reproducibility, limiting clinical translation. Progress requires larger datasets, targeted assays, integration into randomized trials, and GMP-aligned pipelines. We propose a Metabolomics-Derived MSC Potency Index, a standardized metabolite panel benchmarked against functional assays, as a framework for therapeutic readiness. This approach positions metabolomics not as a descriptive tool but as a translational benchmark guiding MSC/EV therapy development. [Image: see text]

Androgenetic alopecia(AGA) is the most common form of hair loss worldwide. By middle age, approximately two-thirds of men and 40% of women are affected. The pathophysiology of AGA involves complex interactions among genetic predisposition, androgen sensitivity, and dysregulation of the hair follicles (HFs) cycle. Among the key regulatory pathways, the Wnt/&#x3b2;-catenin signaling pathway plays a central role in maintaining homeostasis of hair follicle stem cell (HFSCs) and dermal papilla cells (DPCs), as well as in promoting the transition to the anagen phase. Endogenous Wnt inhibitors, such as dickkopfs (DKKs) and secreted frizzled-related proteins (sFRPs), are upregulated under the influence of dihydrotestosterone and can modulate canonical Wnt signaling in DPCs and HFSCs via paracrine mechanisms, potentially contributing to the development of AGA. Targeted inhibition of these endogenous negative regulators may therefore represent a promising therapeutic strategy for AGA. This review summarizes current insights into the role of Wnt signaling in hair follicle biology, the characteristics and functions of DKKs and sFRPs in AGA, and their potential as therapeutic targets.

Human granulocyte colony-stimulating factor (G-CSF) is a hematopoietic hormone promoting the growth, proliferation, differentiation and maturation of myeloid and leukocytic lineages. G-csfs have been used to improve granulocyte count in neutropenic patients, reduce the incidence and duration of neutropenia in patients receiving cytotoxic chemotherapy and to mobilize peripheral blood stem cells prior to leukapheresis for using in both autologous and allogeneic hematopoietic cell transplantation. In general, side-effects are mild to moderate and life threatening side-effects like splenic rupture are very rare. We herein, report a case of spontaneous splenic rupture secondary to high-dose G-CSF use (20 mcg/kg/day), in a healthy female allogeneic donor of peripheral-blood stem cell (PBSC) .