Stem Cell Research & Therapy最新文献

{"title":"Efficacy and safety of stem cell therapy for dry eye disease: a systematic review and meta-analysis.","authors":"Kai-Yang Chen, Hoi-Chun Chan, Chi-Ming Chan","doi":"10.1186/s13287-026-04915-8","DOIUrl":"https://doi.org/10.1186/s13287-026-04915-8","url":null,"abstract":"<p><strong>Introduction: </strong>Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by loss of tear film homeostasis, inflammation, neurosensory abnormalities, and epithelial damage. Despite the availability of topical immunomodulators and procedural interventions, a substantial proportion of patients with moderate-to-severe or refractory DED experience persistent symptoms and inadequate ocular surface recovery. Stem cell-based therapies, particularly mesenchymal stem cells (MSCs) and MSC-derived exosomes, have emerged as regenerative and immunomodulatory strategies aimed at restoring epithelial integrity and tear film stability rather than providing solely symptomatic relief. We conducted a systematic review and meta-analysis to evaluate the clinical efficacy and safety of stem cell and stem cell-derived therapies in human DED.</p><p><strong>Methods: </strong>This study followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420251057372). Six databases were searched from inception to May 14, 2025. Eligible studies were peer-reviewed human clinical investigations evaluating stem cell-based interventions for DED and reporting objective efficacy outcomes such as Schirmer test, tear break-up time (TBUT), corneal fluorescein staining (CFS), or patient-reported outcomes including the Ocular Surface Disease Index (OSDI). Pooled mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Statistical heterogeneity was assessed using the I² statistic. Risk of bias was evaluated using RoB 2 for randomized controlled trials and ROBINS-I for non-randomized studies.</p><p><strong>Results: </strong>Six studies comprising 131 patients were included. Stem cell-based therapies demonstrated significant improvements in tear production, tear film stability, epithelial integrity, and symptom burden. Schirmer test improved by MD = 4.70 mm (95% CI, 4.18-5.22; p < 0.001; I² = 12.59%), indicating a consistent enhancement of aqueous tear secretion. TBUT showed a large standardized improvement with pooled SMD = 1.125 (95% CI, 0.821-1.428; p < 0.001), although randomized trials demonstrated smaller effect sizes than non-randomized studies. OSDI scores decreased by MD = -11.44 points (95% CI, -22.71 to -0.17; p = 0.047), reflecting symptomatic improvement but with substantial between-study variability. Corneal fluorescein staining decreased by MD = -1.04 (95% CI, -1.23 to -0.84; p < 0.001; I² = 0%), supporting epithelial recovery. No serious treatment-related adverse events were reported; however, safety reporting was heterogeneous and follow-up durations were limited.</p><p><strong>Conclusion: </strong>Stem cell and stem cell-derived therapies are associated with significant improvements in both objective and subjective outcomes in DED and demonstrate a favorable short-term safety profile. Nevertheless, heterogeneity in cell source, delivery route, dosage, and stu","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional development of photoreceptors in human retinal organoids.","authors":"Yue Zhang, Mingxia Du, Yi-Han Wang, Min Li, Kangxin Jin, Deng Pan, Xiao Zhang, Zi-Bing Jin","doi":"10.1186/s13287-026-05027-z","DOIUrl":"https://doi.org/10.1186/s13287-026-05027-z","url":null,"abstract":"<p><strong>Background: </strong>Retinal organoids (ROs) derived from human pluripotent stem cells are crucial for modeling retinal development and disease. However, the functional electrophysiological maturation of photoreceptors within ROs remains poorly characterized. This study aimed to define the functional maturation timeline of photoreceptors in human embryonic stem cell (hESC)-derived ROs.</p><p><strong>Methods: </strong>H9 hESC-derived ROs which included a CRX-tdTomato reporter line for specific photoreceptor identification were utilized. An integrated approach of RNA-sequencing analysis, immunofluorescence staining, and whole-cell patch-clamp recordings was employed to systematically assess photoreceptor maturation over 300 days of differentiation.</p><p><strong>Results: </strong>Transcriptional and protein analysis revealed progressive upregulation of key ion channels. Patch-clamp recordings demonstrated stage-dependent maturation of membrane properties, which stabilized by D120-125. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents (I_h) increased progressively, peaking at D240, with amplitudes comparable to mature primate photoreceptors. Voltage-gated sodium (Nav) currents also showed significant developmental upregulation, reaching a maximum, stable plateau from D210-215 onward. Pharmacological blockade confirmed the identity of HCN and Nav currents. Critically, the capacity for action potential (AP) generation increased developmentally, with the proportion of photoreceptors capable of firing APs rising from 16.7% at D90-95 to a peak of 90.2% by D240-245.</p><p><strong>Conclusions: </strong>This study defines a comprehensive electrophysiological maturation timeline for photoreceptors in human ROs and establishes D240 as a key benchmark for functional maturity, characterized by peak I_h currents and AP generation capacity equivalent to mature native photoreceptors. These findings provide essential physiological criteria for standardizing RO quality control, enhancing their utility for modeling retinal degenerative diseases and developing cell replacement therapies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-driven biomedical technologies for tooth regeneration: engineering scaffolds, organoid models, and molecular targeted strategies.","authors":"Zhaorui Jin, Bo Yang, Siyuan Zhang, Zhi Liu, Yuhao Wang, An Lin, Kexin Yang, Mei Yu, Weidong Tian, Fangjun Huo","doi":"10.1186/s13287-026-05044-y","DOIUrl":"https://doi.org/10.1186/s13287-026-05044-y","url":null,"abstract":"<p><p>Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial-mesenchymal interactions and enable controlled reconstruction of dentin-pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell-material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cells targeting fibroblast activation protein eliminate pathological fibroblasts and preserve cardiac function in a Duchenne Muscular Dystrophy murine model.","authors":"Céline Marigny, Gaëlle Revet, Anne Berger, Morgane Boulch, Nathalie Mougenot, Zhenlin Li, Béatrice Corre, Mégane Lemaitre, Axelle Bois, Clara Castelli, Victor Collombat, Ara Parlakian, Marie-Cécile Perier, Adrian Bot, Jonathan A Epstein, Peggy Lafuste, Albert Hagege, Haig Aghajanian, Clément Cochain, Philippe Bousso, Onnik Agbulut, Philippe Menasché","doi":"10.1186/s13287-026-05025-1","DOIUrl":"https://doi.org/10.1186/s13287-026-05025-1","url":null,"abstract":"<p><strong>Background: </strong>Chimeric Antigen Receptor (CAR)-T cells therapy has revolutionized the treatment of hematological cancers and are currently redirected towards non-malignant diseases. If correction of the gene defect remains the cornerstone of the treatment of Duchenne Muscular Dystrophy (DMD), the disease-associated fibrosis can limit its efficacy. We thus assessed the effects of eliminating cardiac fibrosis of DMD by CAR-T cells targeting Fibroblast Activation Protein (FAP), a protein strongly expressed by activated fibroblasts.</p><p><strong>Methods: </strong>In vitro CAR-T cells expressing both FAP and a green fluorescent probe (GFP) were first co-cultured with FAP + of FAP- target cells to check for FAP-expressing lymphocyte activation. Then, anti-FAP CAR-T cells were intravenously delivered in a dystrophic murine model (D2.mdx), following lymphodepletion, to investigate the kinetics, biodistribution, cardiac functional and anti-fibrotic effects of anti-FAP CAR-T cells compared with control lymphocytes engineered to only express GFP. The mechanism of action at a cellular level was assessed by single-cell RNA-sequencing of harvested hearts.</p><p><strong>Results: </strong>In vitro anti-FAP CAR-T cells were successfully activated when co-cultured with FAP + target cells. In a dystrophic murine model (D2.mdx), anti-FAP CAR-T cells, intravenously delivered following lymphodepletion, homed to the heart and skeletal muscles, where they decreased FAP and fibrosis-associated genes. Single-cell RNA-sequencing linked these changes to a decrease in a definite cluster of fibrogenic fibroblasts. Concomitantly, anti-FAP CAR-T cells improved cardiac function compared to control mice injected with GFP-transduced T lymphocytes or bovine serum albumin used as negative controls.</p><p><strong>Conclusions: </strong>These results suggest that anti-FAP CAR-T cells could be efficient for mitigating fibrosis and thus complement gene therapy of DMD. More generally, their therapeutic benefits pave the way for potential applications extending to other fibrosis-associated diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-armored mesenchymal stem cells potentiate antitumor immunity to combat ovarian cancer.","authors":"Minghui Cao, Yingmei Tang, Yunhua Li, Jianing Li, Minxi Shen, Lanxin Hu, Yingni Zhang, Dongye Li, Dongye Wang, Jiaji Mao, Jun Shen","doi":"10.1186/s13287-026-05028-y","DOIUrl":"https://doi.org/10.1186/s13287-026-05028-y","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies often resistant to immune checkpoint blockade (ICB) due to poor infiltration of cytotoxic CD8⁺ T cells and type 1 conventional dendritic cells (cDC1s) into the tumor microenvironment (TME). To overcome this, we engineered magnetic resonance imaging (MRI)-visible mesenchymal stem cells (MSCs) to co-express interleukin-15 (IL-15) for T-cell activation and XC motif chemokine ligand 1 (XCL1) for cDC1 recruitment, aiming to remodel the TME and enhance therapeutic outcomes.</p><p><strong>Methods: </strong>MSCs were engineered via lentiviral transduction to stably express Il15, Xcl1, and a ferritin reporter for MRI tracking. In vitro validation included assays for gene expression, cytokine secretion, T-cell proliferation, and DC migration. Therapeutic efficacy was evaluated in subcutaneous (ID8) and disseminated (intraperitoneal FLUC-eGFP-ID8 and intra-omental FLUC-eGFP-OVHM) murine OC models. Mice received peritumoral (subcutaneous model) or intraperitoneal (disseminated models) injections of engineered MSCs (1×10⁷ cells). Anti-PD-1 antibody (10 mg/kg, twice weekly) was administered intraperitoneally in disseminated models. Tumor progression was monitored by MRI, bioluminescence imaging, and survival analysis. Immune cell infiltration and phenotypes were assessed using flow cytometry, qPCR, immunofluorescence, and immunohistochemistry.</p><p><strong>Results: </strong>Engineered MSCs sustainably secreted IL‑15 and XCL1, enhancing T cell proliferation and cDC1 migration in vitro. In vivo MRI confirmed efficient MSCs homing to subcutaneous tumors, suppressing tumor growth. In disseminated models, multi-armored MSC therapy inhibited tumor progression and prolonged survival, with combination therapy achieving superior outcomes. Mechanistically, this treatment drove a robust infiltration of CD8⁺ T cells and cDC1s into the TME. Flow cytometry revealed a beneficial shift in the CD8⁺ T-cell compartment toward progenitor-like, proliferative, and effector phenotypes. Furthermore, tumor-infiltrating cDC1s displayed elevated expression of co-stimulatory molecules CD80 and CD86, indicating enhanced activation.</p><p><strong>Conclusions: </strong>MRI-visible MSCs co-expressing IL-15 and XCL1 effectively target ovarian tumors and remodel the immune microenvironment to foster potent anti-tumor immunity. By recruiting activated cDC1s and promoting durable, functional CD8⁺ T-cell responses, these multi-armored MSCs synergize with ICB to overcome therapeutic resistance. This cellular immunotherapy represents a promising strategy for ICB-resistant OC and warrants clinical translation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized clinical trial comparing intra-articular injection of bone marrow aspirate clot and bone marrow aspirate concentrate in grade 3 and 4 knee osteoarthritis.","authors":"José Fábio Lana, Luyddy Pires, Alex Macedo, Sérgio Mainine, Tomas Mosaner, Daniel de Moraes Ferreira Jorge, Gabriel Azzini, Lucas Furtado da Fonseca, Claudia Herrera Tambeli, Marco Antônio Percope de Andrade","doi":"10.1186/s13287-026-05041-1","DOIUrl":"10.1186/s13287-026-05041-1","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a degenerative joint condition characterized by progressive cartilage deterioration and chronic pain, leading to functional impairment. Bone marrow-derived orthobiologics, such as bone marrow aspirate clot (BMA-clot) and bone marrow aspirate concentrate (BMAC), have emerged as promising regenerative therapies. Despite their growing clinical use, no randomized clinical trials to date have directly compared the efficacy and safety of these two approaches in patients with KOA, leaving a gap in the current evidence base. This study aimed to compare the efficacy and safety of intra-articularBMA-clot and BMAC in patients with moderate to severe KOA over a 12-month follow-up period. In this prospective, randomized, double-blind clinical trial, patients aged 50-80 years with Kellgren-Lawrence grade 3-4 KOA were enrolled. Participants received thr ee monthly intra-articular injections of eitherBMA-clot or BMAC. The primary outcome was functional improvement assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included pain reduction (Visual Analog Scale) and quality of life (Short Form-36, SF-36). Adverse events were monitored, and data were analysed using mixed-effectsmodels. Both treatments resulted in significant improvements in pain, function, and quality of life throughout the 12-month period. Clinical outcomes between the BMA-clot and BMAC groups were not statistically different. The incidence of adverse events was low, with no serious complications observed. Intra-articular administration of BMA-clot and BMAC appears to be safe and effective for the management of moderate to severe KOA, providing sustained symptom relief and functional gains over a 12-month period. Given its simpler preparation and lower cost, BMA-clot may represent a more accessible therapeutic option in clinical settings.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from BMSCs regulate macrophage M1/M2 polarization and promoting tendon-bone healing through circRNA1052.","authors":"Guorong Wang, Juntao Xu, Zhuo Chen, Zichen Wang, Yizhou Lin, Xiaoliang Xu, Qian Lu, Qinguang Xu, Yifan Sun, Li Chen, Long Xu, Xiongfeng Li, Fengfeng Wu","doi":"10.1186/s13287-026-05042-0","DOIUrl":"https://doi.org/10.1186/s13287-026-05042-0","url":null,"abstract":"<p><strong>Background: </strong>The high retear rate post tendon-bone reconstructive surgery is attributed to scar tissue replacing fibrocartilage, which compromises mechanical properties. Macrophages play a pivotal role in this process. Bone marrow mesenchymal stem cells-derived exosome (BMSCs-Exo) have emerged as a promising biological therapeutic approach. However, their role and underlying mechanisms in regulating macrophage polarization and tendon-bone healing require further investigation.</p><p><strong>Methods: </strong>Primary macrophages were cultured, and a rat Achilles tendon-calcaneus reconstruction model was established, followed by BMSCs-Exo treatment. Exosome diameter was analyzed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Macrophage polarization was assessed via flow cytometry and immunofluorescence. ELISA measured cytokine levels, and immunohistochemistry evaluated molecular expression and distribution. Apoptosis levels were analyzed using TUNEL staining, and HE as well as Safranin O-Fast Green staining were utilized to examine tissue morphology and fibrocartilage regeneration at the tendon-bone junction. Biomechanical testing was used to assess joint stability. Western blot assessed molecular expression, while circRNA-seq was conducted to explore the impact of BMSCs-Exo on circRNA expression profiles in tendon-bone junction macrophages. qRT-PCR quantified circRNA and linear RNA levels, and fluorescence in situ hybridization (FISH) was used to observe circRNA expression and localization.</p><p><strong>Results: </strong>We isolated BMSCs-Exo and discovered its ability to promote macrophage polarization from M1 to M2 both in vitro and in vivo. This polarization was accompanied by a decrease in pro-inflammatory cytokines IL-1β and IL-12, and an increase in anti-inflammatory cytokines TGF-β1 and IL-10. Additionally, BMSCs-Exo significantly enhanced tendon-bone healing, improved the tissue morphology at the tendon-bone junction, increased chondrocyte and fibrocartilage formation, upregulated the expression of collagen I, Aggrecan, and collagen II, improved joint stability. However, macrophage depletion using Clodronate liposomes (CL) effectively inhibited the therapeutic effects of BMSCs-Exo. Mechanistic studies revealed that BMSCs-Exo transfers circRNA1052 to macrophages, driving their polarization from M1 to M2, thereby mitigating early inflammatory responses and enhancing tissue repair during later stages, ultimately facilitating tendon-bone healing. Furthermore, downregulation of circRNA1052 expression attenuated the beneficial effects of BMSCs-Exo.</p><p><strong>Conclusions: </strong>BMSCs-Exo transfer circRNA1052 to macrophages, suppressing their pro-inflammatory phenotype and promoting polarization toward the tissue-repairing M2 phenotype. This process enhances fibrocartilage formation, improves tissue morphology, and accelerates tendon-bone healing.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage autophagy-dependent M2 polarization mediates the protective effect of ADSC-conditioned medium against acute lung injury.","authors":"Jiachen Li, Fan Yang, Ziyi Ren, Chuanyu Zhang, Mingwei Xing, Zhihui Jiao","doi":"10.1186/s13287-026-04981-y","DOIUrl":"https://doi.org/10.1186/s13287-026-04981-y","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived mesenchymal stem cell conditioned medium (ADSC-CM) has emerged as a promising cell-free therapeutic strategy for acute lung injury (ALI). ADSC-CM's anti-inflammatory effect is closely related to its ability to regulate alveolar macrophage polarization. Furthermore, autophagy in macrophages is considered to be related to the regulation of polarization. However, the specific role and mechanisms by which ADSC-CM coordinates autophagy to guide macrophage polarization are not yet fully clear and urgently require further research.</p><p><strong>Methods: </strong>We established an in vivo rat model of LPS-induced ALI to evaluate the ameliorative effects of ADSC-CM. Concurrently, an in vitro model utilizing NR8383 alveolar macrophages was employed to investigate the underlying mechanisms. A comprehensive suite of techniques, including ELISA, flow cytometry, immunohistochemistry, Western blot, and RT-qPCR, was applied for analysis.</p><p><strong>Result: </strong>In in vivo experiments, ADSC-CM treatment significantly alleviated LPS-induced pneumonia. In vitro experiments revealed that ADSC-CM enhanced the autophagic flux in NR8383 cells and effectively counteracted the promotion of LPS-driven M1 pro-inflammatory phenotypes, while inducing a shift toward M2 anti-inflammatory phenotypes. This beneficial polarization was proven to be dependent on autophagy, as it was significantly reduced when autophagy was inhibited. Mechanistically, autophagy mediated by ADSC-CM was shown to regulate the STAT1/STAT6 signaling pathway and influence HIF-1α expression.</p><p><strong>Conclusion: </strong>Our research results indicate that ADSC-CM alleviates ALI by targeting alveolar macrophages. Its protective mechanism involves enhancing autophagy activity, thereby promoting the polarization of macrophages towards the M2 phenotype through the regulation of STAT1/STAT6 and HIF-1α pathways. This study reveals the immunomodulatory role of ADSC-CM dependent on autophagy, highlighting its potential as an acellular therapeutic strategy for treating ALI.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced regenerative solutions in diabetic foot ulcer therapy: delivery of mesenchymal stem cells in injectable hydrogels.","authors":"Seyed Amir Sadrzadeh, Maryam Ranjbar, Mohammad Javad Entezari Meybodi, Yasmin Khorram, Mahsa Sani, Mona Latifi, Farnaz Sani","doi":"10.1186/s13287-026-05036-y","DOIUrl":"https://doi.org/10.1186/s13287-026-05036-y","url":null,"abstract":"<p><p>Diabetic foot ulcers (DFUs) are a severe complication of diabetes characterized by impaired healing driven by oxidative stress, chronic inflammation, reduced angiogenesis, and neuropathy, leading to high risks of infection and amputation. Current therapies remain insufficient, necessitating advanced regenerative approaches. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential through immunomodulation, angiogenesis, and extracellular matrix remodeling; however, their clinical application is limited by poor survival and retention, as well as potential safety concerns. Increasing evidence indicates that MSC-derived exosomes play a central role in mediating these therapeutic effects via paracrine signaling, delivering bioactive cargos such as microRNAs, proteins, and cytokines that regulate immune responses, angiogenesis, and tissue regeneration with lower immunogenicity and improved stability compared to cell-based therapies. Injectable hydrogels have emerged as biomimetic platforms that not only enhance MSC viability and retention but also provide an optimal delivery system for exosomes by protecting them from degradation and enabling sustained, localized release within the wound microenvironment. The integration of MSC-derived exosomes with hydrogel systems represents a synergistic strategy that simultaneously addresses multiple pathological barriers in DFUs, including inflammation, oxidative stress, and impaired vascularization. This review highlights recent advances in hydrogel-based delivery systems for MSCs and, importantly, MSC-derived exosomes, with a particular emphasis on their combined therapeutic potential in diabetic wound healing. Furthermore, emerging smart and stimuli-responsive hydrogels are discussed as next-generation platforms for optimizing exosome delivery and improving clinical outcomes in DFUs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of fibrosis in human kidney organoids delineates mechanisms and therapeutic targets of fibrotic kidney disease.","authors":"Markus C Doeser, Julia Raimann, Maren Beuke, Zeynep Kilcan, Amélie F Menke, Barbara M Klinkhammer, Peter Boor, Hans R Schöler, Hermann Pavenstädt","doi":"10.1186/s13287-026-05030-4","DOIUrl":"10.1186/s13287-026-05030-4","url":null,"abstract":"<p><strong>Background: </strong>Developing regenerative therapies to restore kidney function in patients with progressive renal disease represents a major challenge for modern molecular nephrology. Kidney organoids, three-dimensional kidney-like structures, which can now be generated by the directed differentiation of human pluripotent stem cells, have emerged as a powerful tool to study kidney development, physiology, and mechanisms of renal disease in vitro. Ultimately, kidney organoids may serve as an experimental platform to unravel the pathomechanisms of renal fibrosis and to test regenerative treatment approaches targeting fibrotic kidney diseases. However, the fibrotic phenotype in kidney organoids and its utility as a disease model remain to be fully characterized.</p><p><strong>Methods: </strong>Three-dimensional self-organizing kidney organoids containing nephrons and stromal cells were exposed to TGF-β1 cytokine to induce fibrotic remodeling. Organoids were analyzed by RNA sequencing and histology.</p><p><strong>Results: </strong>Activation of TGF-β1 signaling in kidney organoids induced hallmarks of human kidney fibrosis, such as tubular atrophy, glomerulosclerosis, and interstitial fibrosis. RNA sequencing highlighted differential regulation of key pathways in kidney fibrosis: epithelial-to-mesenchymal transition, inflammation, metabolism, and JAK/STAT signaling. We identified candidate mediators of kidney fibrosis such as the JAK-STAT downstream target PIM1. Inhibition of PIM1 with the small molecule AZD1208 attenuated fibrosis development in the organoids.</p><p><strong>Conclusions: </strong>Kidney organoids are an amenable system for modeling kidney fibrosis and may guide therapeutic discovery.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}