Stem cells and development最新文献

{"title":"Cancer Stem Cells as Dynamic Attractor States: Systems Biology of Tumor Plasticity and Therapy Resistance.","authors":"Mahendra Aryal","doi":"10.1177/15473287261458681","DOIUrl":"10.1177/15473287261458681","url":null,"abstract":"<p><p>The cancer stem cell (CSC) paradigm has evolved from a rigid hierarchical model to a systems-level perspective in which stemness is a reversible and context-dependent phenotype. Evidence from lineage tracing and single-cell/spatial multiomics indicates that tumor cells occupy continuously evolving phenotypic states governed by complex gene regulatory networks. Within this landscape, CSCs can be interpreted as metastable attractors maintained through coupled signaling, epigenetic, metabolic, transcriptional, and microenvironmental interactions. Tumor heterogeneity and therapeutic resistance emerge through phenotypic reprogramming, regulatory network rewiring, and niche-dependent stabilization under environmental and therapeutic stress. This reframes resistance as an emergent property of tumor ecosystems, underscoring the limitations of targeting static CSC populations or single pathways. Therefore, durable therapeutic control will require network-oriented interventions capable of reshaping attractor topology and disrupting stemness-supportive microenvironments.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"237-246"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Puromycin-Induced Podocyte Injury and Protective Effects of Voclosporin Using Induced Pluripotent Stem Cells from a Patient with Nephrotic Syndrome Harboring an <i>INF2</i> Variant.","authors":"Akihito Tanaka, Kazuhiro Furuhashi, Saki Sakamoto, Asuka Horinouchi, Kumiko Fujieda, Jun Matsumoto, Keita Hattori, Chikao Onogi, Tomohiro Kawazoe, Akihisa Kato, Yu Watanabe, Eri Koshi-Ito, Kayaho Maeda, Hangsoo Kim, Noritoshi Kato, Shoichi Maruyama","doi":"10.1177/15473287261460636","DOIUrl":"10.1177/15473287261460636","url":null,"abstract":"<p><p>Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and end-stage kidney disease (ESKD). Many cases are attributable to pathogenic variants in podocyte-related genes, such as inverted formin 2 (<i>INF2</i>). However, no specific treatment exists for hereditary FSGS, and experimental platforms that faithfully model podocyte injury remain limited. Therefore, in this study, we developed an injury model by generating induced pluripotent stem cells (iPSCs) from a patient with <i>INF2</i>-associated FSGS and differentiating them into kidney organoids. Podocytes were validated by immunofluorescence staining for podocyte-specific markers. We induced podocyte injury in this model using puromycin aminonucleoside (PAN) in a dose-dependent manner. Injury severity was quantified by measuring podocalyxin fluorescence intensity. Cyclosporine A (CsA) or voclosporin (VCS) was administered as a 1-h pretreatment before PAN exposure to evaluate their podocyte-protective effects. The kidney organoids exhibited well-defined podocyte marker expression, confirming successful differentiation. PAN exposure caused a significant and concentration-dependent reduction in podocalyxin fluorescence, indicating robust induction of podocyte injury in organoids harboring the <i>INF2</i> variant. Pretreatment with CsA or VCS significantly attenuated PAN-induced podocyte injury and preserved podocyte marker expression. CsA and VCS reduced podocyte injury to similar extents. In conclusion, we established a patient-specific kidney organoid model of <i>INF2</i>-associated FSGS that reliably recapitulated podocyte vulnerability to toxic injury. This platform demonstrated that calcineurin inhibitors, including the novel agent VCS, exert direct podocyte-protective effects in a genetic FSGS background and provide a practical system for mechanistic studies and therapeutic screening.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"263-269"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Preconditioning Reprograms Mesenchymal Stromal Cell-Derived Extracellular Vesicles into Distinct Functional States for Immunomodulation and Wound Healing.","authors":"Ramiro A Villarreal-Leal, Oscar S Velazquez, Beck Burgelin, Robin S Vander Pol, Corrine Ying Xuan Chua, R Steven Conlan, Richard H Finnell, Alessandro Grattoni, Bruna Corradetti","doi":"10.1177/15473287261456137","DOIUrl":"10.1177/15473287261456137","url":null,"abstract":"<p><p>Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are emerging as potent cell-free mediators of tissue repair, whose composition and function can be tuned by the cellular microenvironment. Although inflammatory cues modulate mesenchymal stromal cell (MSC) behavior, how defined preconditioning strategies program extracellular vesicle (EV) functional outputs remains incompletely understood. Here, we systematically evaluated how priming bone marrow-derived MSCs with interferon-gamma/tumor necrosis factor-alpha (I/T) or lipopolysaccharide (LPS) generates EV populations with distinct immunomodulatory and regenerative properties. Using a murine full-thickness wound model, we performed an integrative analysis of biodistribution, immune response, and extracellular matrix (ECM) remodeling, complemented by single-cell, transcriptomic, and proteomic profiling. All EV populations were retained at the wound site following subcutaneous delivery and supported wound contraction; however, they drove distinct, treatment-specific repair trajectories. I/T-EVs promoted a coordinated regenerative response characterized by balanced macrophage (MΦ) activation, controlled immune modulation, and efficient resolution of inflammation, resulting in organized ECM remodeling. In contrast, LPS-EVs induced a more pro-inflammatory response, accelerating wound contraction and promoting compensatory matrix stiffening with reduced structural coordination. Control EVs primarily facilitated early immune resolution with limited induction of regenerative remodeling pathways. Proteomic profiling of EVs identified enrichment of proteins associated with insulin-like growth factor signaling, MΦ recruitment, and ECM remodeling, consistent with <i>in vivo</i> protein expression patterns and linking EV cargo to functional outcomes. These findings demonstrate that preconditioning does not uniformly enhance EV efficacy but instead selectively programs distinct MSC-EV functional states, establishing EV preconditioning as a tunable strategy for engineering cell-free therapeutics with predictable and context-specific therapeutic outcomes.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"247-262"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic Stem Cell-Based Cell and Gene Therapy Beyond Monogenic Diseases.","authors":"Masayuki Kai, Fulvio Mavilio","doi":"10.1177/15473287261444631","DOIUrl":"10.1177/15473287261444631","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are multipotent stem cells capable of differentiating into all types of blood and immune progeny and endowed with self-renewal capacity to enable lifelong hematopoiesis. Based on these unique characteristics, HSCs are utilized as a cell source for cell and gene therapies. During its dawning period, HSC-based therapies faced significant challenges due to inefficient gene transfer and insertional leukemogenesis. However, technological advances, such as the use of HIV-derived lentiviral vectors and cellular promoters, have established HSC gene therapy as a powerful treatment modality for patients with congenital monogenic diseases, leading to approved therapies commercially available in Europe and the United States. HSC-based therapies are now being explored for broader indications, including cancer, autoimmune, and infectious diseases. Innovative concepts achievable with HSCs-such as delivering therapeutic proteins to hard-to-reach tissues, in vivo delivery of antibodies and immune cells, and molecular shielding-have been proposed, offering new therapeutic approaches. Moreover, technological innovations in related fields, including more precise gene expression control and reduced-toxicity bone marrow conditioning, are expanding the range of applications. HSC-based cell and gene therapies are therefore evolving into a therapeutic modality applicable beyond monogenic diseases to a broader range of indications, to provide therapeutic value to patients with intractable diseases.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"201-211"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OCT3/4-Enhanced Dental Mesenchymal Stem Cells Acquire Hematopoietic Stem Cell-Like Properties and Support Hematopoietic Recovery in a Myelosuppressed Mouse Model.","authors":"Jang-Ho Han, Sang-Yun Lee, Chan-Hee Jo, Young-Bum Son, Won-Jae Lee, Hyeon-Jeong Lee, Chae-Yeon Hong, Sanghyeon Park, Seo-Yoon Kang, Tae-Sung Hwang, Jaemin Kim, Sung-Lim Lee, Yong-Ho Choe, Gyu-Jin Rho","doi":"10.1177/15473287261452516","DOIUrl":"10.1177/15473287261452516","url":null,"abstract":"<p><p>Hematopoietic stem cell (HSC) transplantation is an established therapy for malignant and nonmalignant hematologic disorders; however, clinical application remains constrained by limited graft availability and challenges in maintaining stemness during ex vivo manipulation, as well as transplant-related complications. Accordingly, alternative strategies to generate hematopoietic-competent cells from accessible stem cell sources are being actively explored. This study investigated whether <i>OCT3/4</i> overexpression enhances the hematopoietic trans-differentiation potential of dental tissue-derived mesenchymal stem cells (DMSCs) and whether the resulting HSC-like cells exert therapeutic effects in a cyclophosphamide-induced myelosuppressed mouse model following intra-femoral delivery. <i>OCT3/4</i> was introduced into DMSCs using the Neon transfection system, and <i>OCT3/4</i>-overexpressing DMSCs (DMSCs^OCT3/4+) were subsequently exposed to hematopoietic cytokines to induce an HSC-like phenotype. Cytokine-treated DMSCs^OCT3/4+ exhibited a rounded morphology, increased expression of HSC-associated surface markers (CD34 and CD45), and upregulated hematopoietic transcription factors, including <i>GATA2</i>, <i>C/EBPα</i>, <i>RUNX1</i>, and <i>SCL</i>. The derived HSC-like cells (D-HSCs) were transplanted into the femoral bone marrow cavity of myelosuppressed mice, and therapeutic outcomes were assessed by complete blood counts and histological analyses. D-HSC transplantation was associated with recovery of bone marrow cellularity and partial restoration of spleen and thymus cellularity and size, accompanied by improvement in body weight and peripheral blood parameters compared with myelosuppressed controls. Collectively, these findings indicate that <i>OCT3/4</i>-enhanced DMSCs can be directed toward an HSC-like state under hematopoietic cues and that the resulting cells may support hematopoietic and immune recovery in myelosuppressed hosts, supporting their potential as an alternative, autologous cell source for hematopoietic regeneration.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"212-221"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simplified Derivation of Stable Early Passage Murine Embryonic and Parthenogenetic Stem Cells.","authors":"Erez Pery, Maria G Gervasi, Alex Hauser, Scott Leppanen, Ann A Kiessling","doi":"10.1177/15473287261450907","DOIUrl":"10.1177/15473287261450907","url":null,"abstract":"<p><p>Aneuploidy in cultured embryonic stem (ES) cells severely limits research and therapeutic potential. To begin to understand when chromosomal imbalances arise, primary ES cell lines were derived in feeder-free, fully defined culture media from 44% of two-cell CF1 embryos (5 lines), 37% of CF1 multi-drug resistance (<i>Mdr1</i>/<i>Abcb1</i>) mutant embryos (19 lines), and 2 parthenogenetic stem (mPS) lines from <i>Mdr1</i> mutant eggs for array comparative genomic hybridization analysis. By passage 2, trivial somatic chromosome euploidy was detected in all wild-type lines and in 9 (64%) of the 14 mutant cell lines. Five <i>Mdr1</i> mutant ES cell lines and both mPS cell lines exhibited mosaic gain of chromosome 8 in at least 30% of cells, a common finding in mouse ES cells. X chromosomes exhibited more aneuploidy than somatic chromosomes. Five of the <i>Mdr1</i> mutant lines were male, while the nine female ES cell lines and both mPS lines exhibited almost complete loss of one X chromosome. Two ES lines analyzed at passage 3 exhibited partial gains and losses in chromosomes 15 and 19, suggesting that aneuploidy in murine ES cells begins by passage 3 in standard culture conditions. The somatic cell euploidy in early passage wild-type CF1 ES lines, in contrast to the early accumulation of chromosome 8 triploidy in the <i>Mdr1</i> mutant lines, suggests that component(s) of the culture system not well tolerated by ES cells with the <i>Mdr1</i> mutation may be responsible for triploid chromosome 8 in multipassaged mouse ES cells. The ease of deriving euploid mouse stem cell lines in fully defined culture conditions from individual females encourages the use of primary ES cell lines for a variety of purposes. Adjusting culture components to correct early chromosome 8 accumulation in primary <i>Mdr1</i> mutant lines may reveal pathways critical to maintaining euploidy in cultured ES cells.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"222-231"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> Study of Triiodothyronine Effects on C57B6J Mesenchymal Stem Cells Isolated from Bone Marrow and Adipose Tissue.","authors":"Luigi Marino, Khadija B Danazumi, Marianna Marino, Francesco S Celi","doi":"10.1177/15473287261440389","DOIUrl":"10.1177/15473287261440389","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the ability to differentiate into several cell types that hold great promise for therapeutic applications. However, the maintenance of proliferative and stemness capacity following <i>in vitro</i> expansion remains a significant challenge. Triiodothyronine (T3) plays a crucial role in embryogenesis and fetal development, yet the knowledge of its effects on MSCs' survival and function is limited. Here, we investigate the impact of T3 treatment in bone marrow (BM)-MSCs and adipose tissue (AT)-MSCs isolated from C57BL/6J mice, to assess stemness preservation, proliferation, and gene expression during <i>in vitro</i> expansion. To this end, MSCs were treated with T3 at various concentrations for 24 and 48 h, and thyroid hormone-responsive and stemness-related genes expression, proliferation, clonogenic potential, and surface marker profiles were analyzed using reverse transcript quantitative PCR, Cell Counting Kit-8, colony-forming unit-fibroblast assays, and flow cytometry. Our results show that T3 exposure did not affect variability or clonogenic potential of BM-MSCs and AT-MSCs, and the expression of T3-responsive genes is activated by distinct time- and dose-dependent responses to T3 in AT-MSCs and BM-MSCs. However, in BM-MSCs, a transient increase in pluripotent markers was observed. Conversely, AT-MSCs exhibited sustained increases in <i>Nano-g</i>, <i>Sca-1</i>, and <i>Ssea-1</i>, particularly at 10 and 100 nM. Collectively, we observed that T3 exposure during <i>in vitro</i> expansion enhanced stemness features in MSCs. This finding was more prominent in AT-MSCs compared with BM-MSCs. The data suggest that T3 exposure during AT-MSCs expansion could be a valuable tool to increase the yield and stemness of these MSCs, facilitating their therapeutic use.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"157-166"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Gemcitabine-Induced Autophagy in Cancer-Associated Fibroblasts Reduces Collagen I and Enhances Chemotherapeutic Efficacy in Pancreatic Cancer.","authors":"Dongfeng Song, Hui Tang, Tingting You, Jinrong Ying, Chunmei Bai, Zhao Sun, Qin Han, Robert Chunhua Zhao","doi":"10.1177/15473287261442512","DOIUrl":"10.1177/15473287261442512","url":null,"abstract":"<p><p>In pancreatic cancer, increased collagen I impairs the efficacy of gemcitabine; however, the role of gemcitabine itself in collagen I accumulation remains unclear. This study aims to explore the mechanism of gemcitabine-induced fibrosis and provide new insights to enhance its therapeutic efficacy. We analyzed COL1A1 expression in pancreatic cancer patient tumor tissues and found that gemcitabine treatment upregulated COL1A1 expression. Subsequently, cancer-associated fibroblasts (CAFs) were modeled by inducing human adipose-derived mesenchymal stem cells with tumor-derived exosomes. Using the autophagy inhibitor chloroquine (CQ) and the protein kinase B (AKT) activator SC79, we demonstrated that gemcitabine downregulated P62 expression and upregulated LC3BII, Beclin-1 expression, inducing autophagy in CAFs via decreasing AKT phosphorylation, which further led to collagen I accumulation. In addition, gemcitabine combined with CQ enhanced cell death in both CAFs and tumor cells, while inhibiting tumor cell proliferation and migration. In animal models, this combination therapy reduced gemcitabine-induced autophagy and collagen I deposition, contributing to delayed tumor growth. Collectively, gemcitabine upregulates collagen I by inducing CAF autophagy via reducing AKT phosphorylation. Targeting CAF autophagy can reduce collagen deposition, offering a promising strategy to improve the therapeutic efficacy of gemcitabine in pancreatic cancer.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"167-180"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Aggregate Culture Enhances the Therapeutic Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in the Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Chongxiao Li, Xia Zhou, Erzhuo Xia, Siyuan Tian, Junjie Wang, Gege Fu, Miao Zhang, Shuhao Su, Rui Su, Fangshuo Li, Zheng Qin, Ying Han, Jingbo Wang","doi":"10.1177/15473287261442500","DOIUrl":"10.1177/15473287261442500","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease lacking effective therapies. Mesenchymal stem cells (MSCs) show therapeutic potential; however, their efficacy is often limited. Aggregates of human umbilical cord-derived MSCs (hUC-MSCs) were generated using AggreWell™ 400 plates. The paracrine and mechanotransduction profiles of three-dimensional (3D)-MSCs were assessed by reverse transcription quantitative PCR and western blot. MASH was induced in C57BL/6J mice via a 32-week high-fat, high-fructose, and high-cholesterol (HFFC) diet, followed by tail vein injection of PBS, two-dimensional (2D)-MSCs, or 3D-MSCs. Therapeutic efficacy was evaluated via histological staining, immunohistochemistry, and serum biochemistry. RNA sequencing was performed to elucidate underlying molecular mechanisms. Under 3D culture conditions, hUC-MSCs formed relatively uniform aggregates with preserved MSC phenotypic characteristics after recovery. 3D aggregate culture enhanced the paracrine, anti-inflammatory, mechanosensitive phenotype, pro-survival, and matrix-remodeling properties of hUC-MSCs, evidenced by increased expression of hepatocyte growth factor, tumor necrosis factor-stimulated gene 6, cyclooxygenase-2, prostaglandin E synthase, B-cell lymphoma-2, and mechanotransduction-related genes, accompanied by elevated matrix metalloproteinase-2 (MMP2) and MMP9 expression <i>in vitro</i>. <i>In vivo</i> fluorescence imaging showed no significant difference in early hepatic retention between intravenously infused single-cell hUC-MSCs and 3D aggregates. In the MASH model, 3D-MSCs more effectively reduced lipid accumulation, collagen deposition, α-smooth muscle actin, hepatomegaly, and serum total cholesterol levels compared with 2D-MSCs. Moreover, 3D-MSCs enhanced the expression of anti-inflammatory interleukin-10, while suppressing inducible nitric oxide synthase. 3D-MSC therapy induced broader transcriptional remodeling than conventional MSCs, with enrichment in extracellular matrix organization, focal adhesion, and the phosphatidylinositol 3-kinase-protein kinase B signaling pathway. Consistently, western blot analysis showed that 3D-MSCs more effectively reduced hepatic p-PI3K and p-AKT levels, indicating stronger inhibition of PI3K/AKT pathway activation. 3D aggregate culture enhances the therapeutic efficacy of hUC-MSCs against MASH, supporting its translational potential for MSC-based liver therapy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"181-193"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robotic Rehabilitation after Regenerative Medicine Improves Gait Performance and Brain Connectivity in Chronic Stroke Patients.","authors":"Louis Yuge, Kei Nakagawa, Eiichiro Tanaka, Yumi Kawahara","doi":"10.1177/15473287261436291","DOIUrl":"10.1177/15473287261436291","url":null,"abstract":"<p><p>Regenerative medicine for stroke patients has been attracting attention. However, the effects of rehabilitation after the cell transplantation have not been fully elucidated. The purpose of the present study was to investigate whether intensive gait-focused rehabilitation using a robotic orthosis after regenerative medicine improved gait function and induced plastic changes in cortical networks. The present study was conducted in a retrospective cohort study. We selected seven chronic stroke patients, those who had undergone adipose-derived mesenchymal stem cells (MSC) transplantation therapy after the onset of stroke and had been receiving adequate subsequent gait rehabilitation with a robot for more than 2 months. During hospitalization, each patient received at least 2 h of rehabilitation, including robotic-assisted gait training more than five times per week. As the assessments, gait performance and M1 seed-based resting state-functional connectivity (rs-FC) obtained by a magnetoencephalography were compared before and after hospitalization. After rehabilitation, cadence and spatial gait symmetry ratio were significantly improved, and a significant negative correlation was found between the changes in the gait symmetry ratio and the time from transplant to rehabilitation. Seed-based rs-FC in the beta band between the lesioned M1 and multiple brain regions (e.g., both frontal areas, ipsilateral postcentral gyrus) was significantly decreased after the rehabilitation. Significant negative correlations were also observed between the changes in the gait symmetry ratio and the changes in lesioned M1 seed-based rs-FC in the paracentral gyrus and regions associated with the default mode network. It was revealed that intensive gait-focused rehabilitation using a robotic orthosis improved gait function and induced plastic changes in the cortical networks. The improvements were significantly correlated with the timing of the start of rehabilitation after MSC transplantation.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"135-143"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}