Stem Cell Research & Therapy最新文献

{"title":"Mesenchymal stem cell derived exosomes mitigate COVID-19 cytokine storm via Annexin A1 and TGF-β mediated MAPK pathway inhibition.","authors":"Nesrine Ebrahim, Hajir A Al Saihati, Arigue A Dessouky, Yasmeen Mohammed Ismail, Ashraf A Shamaa, Shereen A Mohamed, Mohamed E Mohamed, Nermine Nosseir, Mohamed Ahmed Eladl, Gianpiero Di Leva, Omnia A Badr","doi":"10.1186/s13287-026-04980-z","DOIUrl":"https://doi.org/10.1186/s13287-026-04980-z","url":null,"abstract":"<p><strong>Background: </strong>Severe COVID-19 is marked by a dysregulated inflammatory response, known as a cytokine storm, resulting in acute respiratory distress syndrome (ARDS) and multiple organ failure. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated potential as immunomodulatory agents. This work investigates the possibility of MSC-Exos to mitigate excessive inflammation in COVID-19 by targeting the mitogen-activated protein kinase (MAPK) signalling pathway.</p><p><strong>Methodology: </strong>We integrated molecular docking analysis between TGF-β and Annexin A1 as exosomal proteins and key component proteins of the MAPK pathway (p38, ERK1/2, JNK1). The in-silico results were then validated in vivo using a Syrian hamster model of SARS-CoV-2 infection. Quantitative PCR (qPCR), western blotting, and histological examination were employed to evaluate the effects of MSC-Exos therapy on MAPK pathway activation, cytokine production, and lung tissue pathology.</p><p><strong>Results: </strong>The in-silico study revealed extensive hydrogen bonding and hydrophobic interactions at the protein-protein interfaces between exosomal proteins and MAPK components. These interactions suggest that exosomal proteins may modulate MAPK signaling pathways. In vivo, MSC-Exos administration led to marked downregulation of pivotal genes in the MAPK signaling pathway (MEKK1, MEKK2, MEKK3), diminished phosphorylation of JNK1, p38, and ERK1/2, and lowered production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Histopathological examination demonstrated ameliorated lung tissue structure, characterized by diminished alveolar wall thickness and decreased immune cell infiltration.</p><p><strong>Conclusion: </strong>MSC-Exos elicit immunomodulatory effects in SARS-CoV-2-Infected hamsters, partially by directly targeting and blocking the MAPK signaling pathway. These findings offer a compelling justification for the clinical assessment of MSC-Exos as a therapeutic approach to alleviate the cytokine storm and enhance outcomes in severe COVID-19 by targeting the ACE2-Independent pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857294","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":"Spatiotemporal single-cell atlas of suture stem cell dynamics in craniosynostosis.","authors":"Xinyan Chen, Chenzhi Lai, Tian He, Zong Chen, Xiaolei Jin","doi":"10.1186/s13287-026-04987-6","DOIUrl":"https://doi.org/10.1186/s13287-026-04987-6","url":null,"abstract":"<p><strong>Background: </strong>Craniosynostosis is a congenital disorder characterized by premature suture fusion and aberrant skull morphogenesis. The cellular dynamics and regulatory mechanisms of suture mesenchymal stem cells (SuSCs) in this disease remain poorly defined.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing and 2-μm-resolution Visium HD spatial transcriptomics to build a spatiotemporal atlas of coronal suture cells in Fgfr2^C342Y/+ mice, a murine model recapitulating human Crouzon syndrome, alongside wild-type controls across three key developmental stages (E14.5, E18.5, and P3). To obtain near single-cell spatial resolution, we created SpatialCell, which combines morphology-based segmentation and machine-learning classification using a reference trained on our single-cell datasets.</p><p><strong>Results: </strong>The atlas reveals stage-specific remodeling of SuSC niches and a shift of SuSC spatial associations toward osteogenic mesenchyme in craniosynostosis. Along the SuSC-to-osteoblast trajectory, pre-osteoblasts were depleted earlier than upstream SuSCs, and SuSCs displayed premature acquisition of osteogenic programs near the suture midline. Temporal Gene Ontology patterns indicated early extracellular-matrix disruption, mid-gestation chondrogenic activation, and postnatal mineralization. Network analysis nominated Foxa3 as a candidate regulator in SuSC subsets; siRNA knockdown of Foxa3 reduced ex vivo mineralization in the craniosynostosis background. Spatial communication analyses implicated signals from suture meningeal fibroblasts and immune cells that converge on SuSC fate.</p><p><strong>Conclusions: </strong>Our results support a model where craniosynostosis may involve disrupted temporal coordination of developmental programs, not merely accelerated bone formation. The atlas and analytic framework pinpoint when and where SuSC fate diverges, propose Foxa3 as an intervention target, and provide a high-resolution resource for mechanistic and therapeutic exploration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820818","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":"Engineered cardiac patches from hiPSC-derived cardiomyocytes.","authors":"Jonas Jawad, Mohammad Z Khan, Tamer Jabsheh, Daryoush Javidi","doi":"10.1186/s13287-026-05007-3","DOIUrl":"https://doi.org/10.1186/s13287-026-05007-3","url":null,"abstract":"<p><strong>Background: </strong>Heart failure remains a leading global cause of morbidity and mortality, with limited capacity for myocardial regeneration following infarction. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a promising therapeutic resource due to their scalability, differentiation potential, and immunologic adaptability. Engineered cardiac patches, three-dimensional constructs of hiPSC-CMs combined with supporting cells and scaffolds, offer a strategy to deliver organized myocardium directly to injured hearts, overcoming the limitations of cell injection therapies.</p><p><strong>Scope of review: </strong>This review synthesizes evidence from 2010 to early 2025, spanning rodent, porcine, and non-human primate models, as well as the first clinical trials of hiPSC-CM patches. We highlight recent advances in maturation protocols, vascularization strategies, and scaffold engineering, while discussing two distinct translational paradigms: short-term paracrine support versus long-term remuscularization under sustained immunosuppression.</p><p><strong>Results: </strong>Preclinical studies show that engineered patches improve graft survival, with engraftment rates ranging from 5 to 15%, alongside enhanced vascularization, electrical coupling, and left ventricular function. In large animal models, patches scaled to clinically relevant sizes achieved durable integration and improved hemodynamics. Of note, arrhythmogenic risk was lower than in intramyocardial injection models. Early human trials in Japan and Germany confirm feasibility and safety, with preliminary evidence of efficacy, including preliminary evidence of improved left ventricular ejection fraction and upgrades in NYHA functional class. Immunogenicity, graft maturation, and manufacturing scalability remain key hurdles, though innovations such as gene-edited hypoimmunogenic lines, multipronged maturation strategies, and bioreactor-based production offer potential solutions.</p><p><strong>Conclusions: </strong>Engineered hiPSC-CM cardiac patches represent a rapidly advancing frontier in regenerative cardiology. While early data indicate technical feasibility and measurable functional benefits, broader adoption will depend on resolving challenges of immune compatibility, arrhythmia prevention, and large-scale manufacturing. With coordinated progress in science, engineering, and regulation, cardiac patches may evolve into a transformative therapy for heart failure.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820835","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":"Generation and single-cell characterization of functional megakaryocytes derived from umbilical cord blood.","authors":"Yanmin He, Yue Liang, Ji He, Yu Shen, Zhipan Wu, Shanshan Pei, Faming Zhu","doi":"10.1186/s13287-026-05047-9","DOIUrl":"https://doi.org/10.1186/s13287-026-05047-9","url":null,"abstract":"<p><strong>Background: </strong>Generation of megakaryocytes (MKs) from stem cells in vitro to produce platelets (PLTs) is an appealing approach for providing an alternative source of PLTs. Understanding the transcriptomic characteristics of MKs in vitro is crucial for providing a theoretical foundation for producing functional MKs more efficiently in the future.</p><p><strong>Methods: </strong>CD34⁺ hematopoietic stem and progenitor cells (HSPCs) were separated from umbilical cord blood (UCB) and were induced to differentiate into MKs in vitro through a culture system. The phenotypes of these cells cultured for different durations were analyzed through flow cytometry. The mRNA expression levels of GATA1, GATA2, FOG1, NF-E2, FLI1, CD41, and CD61 at different time points were analyzed through quantitative PCR. The activation levels of PLTs in vitro and the PLTs produced in vivo were determined. The MK subpopulations were further analyzed through single-cell RNA sequencing (scRNA-seq).</p><p><strong>Results: </strong>UCB-derived MKs exhibited typical characteristics of MKs in vivo, including morphology, polyploidy, and subcellular structure. The mRNA expression levels of GATA1, FOG1, NF-E2, FLI1, CD41, and CD61 on Days 10 and 14 were significantly greater than those on Day 4. CD62P expression on the surface of UCB-PLTs increased markedly in response to thrombin or TRAP6 stimulation. Humanized PLTs were also detected in the peripheral blood of NCG mice following the infusion of UCB-MKs. According to the results of the sc-RNAseq analysis, nine transcriptionally distinct clusters of UCB-MKs, labeled MK1-MK9, were identified, with only the MK9 population being related to immunity. The MK1-MK8 populations displayed typical MK characteristics and were the most prevalent subtypes. In addition, compared with hESCs, UCB-derived MKs exhibited a greater proportion of active-cycling MKs with strong differentiation potential.</p><p><strong>Conclusions: </strong>In conclusion, this study describes the biological functions and transcriptomic profile of MKs derived from UCB, which will aid in the further development of more efficient systems for generating MKs in vitro and promote their application in cellular therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820900","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":"Refined detection of CD34⁺CD38⁻CD45RA⁺ leukemic stem cells using a single-tube flow cytometry assay and its strong association with measurable residual disease in acute myeloid leukemia: a retrospective cohort study.","authors":"Amir Abbas Navidinia, Shahrbanoo Rostami, Najibe Karami, Mohammadreza Shemshadinia, Habibeh Sabri Patekhor, Akram Hajaliaskari, Saeed Mohammadi, Tahereh Rostami, Maryam Barkhordar, Mohammad Vaezi, Ghasem Janbabaei, Bahram Chahardouli","doi":"10.1186/s13287-026-05038-w","DOIUrl":"https://doi.org/10.1186/s13287-026-05038-w","url":null,"abstract":"<p><strong>Background: </strong>Leukemic stem cells (LSCs) are the cellular reservoir most strongly implicated in relapse of acute myeloid leukemia, yet their operational detection by multiparameter flow cytometry remains challenging because of immunophenotypic overlap with normal progenitors and variability across assays. Including CD45RA in the CD34⁺CD38⁻ gating strategy substantially improves discrimination between malignant and normal stem/progenitor populations and thus enables more precise LSC enumeration in a single-tube format. Given the clinical importance of accurately quantifying the LSC compartment, we evaluated a refined single-tube flow cytometry assay that incorporates CD45RA within the CD34 + CD38- gate to increase specificity for the leukemic stem compartment.</p><p><strong>Methods: </strong>In a retrospective cohort of 109 AML bone marrow samples, measurable residual disease (MRD) was assessed with a conventional three-tube, 8-color panel and LSCs were enumerated using an adapted single-tube, 8-color panel defining LSCs as CD34 + CD38-CD45RA + . To ensure analytical reliability we applied a formal lower limit of quantification (LLOQ), defined empirically as a cluster of 50 CD45 + events; samples below the sample-specific LLOQ were not called positive. Positivity thresholds were set at ≥ 0.1% for MRD and ≥ 0.004% for LSCs. Group comparisons used the Mann-Whitney U test and associations were quantified by Pearson correlation.</p><p><strong>Results: </strong>LSCs were detectable in 28/109 (25.7%) patients, while MRD positivity was observed in 37/109 (33.9%) patients. A robust association was demonstrated between LSC presence and MRD positivity (p = 0.00035). The LSC burden was significantly elevated in MRD-positive patients, and concomitantly, MRD levels were profoundly higher in patients harboring detectable LSCs (p = 2.01 × 10⁻⁹). A strong positive correlation was observed between LSC and MRD levels across the entire cohort (R = 0.66, p = 3.2 × 10⁻¹⁵). LSC and MRD status were independent of sex, FLT3, or NPM1 mutation status. Immunophenotypic profiling of the LSC compartment revealed predominant aberrant co-expression of CD33 (89.3%) and a multi-marker cocktail (89.3%), with CD44 (67.9%) and CD123 (53.6%) also frequently observed.</p><p><strong>Conclusions: </strong>The implementation of a refined LSC detection assay, leveraging CD45RA gating and a stringent LLOQ, yields a specific and clinically actionable quantification of the LSC reservoir in AML. The strong correlation between the CD34 + CD38-CD45RA + LSC subset and MRD status suggests its potential as a complementary biomarker for residual disease monitoring; however, prospective validation in outcome-annotated cohorts is required to establish its prognostic utility and clinical applicability.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820891","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":"3D spheroids of umbilical cord-derived MSCs protect retinal pigment epithelium against oxidative and inflammatory injury by activating autophagy.","authors":"Qian Xu, Mengyao Li, Dong Li, Xiaoyu Dai, Yifei Zhang, Yi Qu","doi":"10.1186/s13287-026-05043-z","DOIUrl":"https://doi.org/10.1186/s13287-026-05043-z","url":null,"abstract":"<p><strong>Background: </strong>Age-related macular degeneration (AMD) is characterized by progressive retinal pigment epithelium (RPE) dysfunction driven by oxidative stress and chronic inflammation, in which NLRP3 inflammasome activation plays a critical role. Mesenchymal stem cells (MSCs) exhibit therapeutic potential, but their efficacy is limited by poor survival and reduced paracrine activity in hostile microenvironments. Here, we investigated whether three-dimensional (3D) spheroid culture enhances the protective effects of umbilical cord-derived MSCs (UC-MSCs) on RPE cells by promoting autophagy and suppressing inflammasome activation.</p><p><strong>Methods: </strong>Human UC-MSCs were cultured as 3D spheroids or conventional 2D monolayers and applied in sodium iodate (NaIO₃)-induced oxidative injury models both in vitro and in vivo. Retinal morphology and function were assessed via histology and electroretinography, while NLRP3/caspase-1 activation, LC3-II/I ratios, and autophagy flux were quantified using immunofluorescence and Western blot. GO/KEGG enrichment was performed to identify pathways associated with 3D MSCs efficacy. Mechanistic involvement of autophagy was validated using 3-methyladenine (3-MA) and rapamycin.</p><p><strong>Results: </strong>3D MSCs formed compact spheroids exhibiting enhanced paracrine potential and significantly outperformed 2D MSCs in protecting RPE cells against NaIO₃-induced injury. In vivo, 3D MSC treatment preserved retinal structure, reduced RPE cell loss, and improved retinal function. In vitro, co-culture with 3D MSCs markedly improved ARPE-19 viability, reduced apoptosis, and modulated autophagy-related marker expression, as evidenced by increased LC3-II/I ratios. 3D MSCs significantly inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine release, effects reversed by 3-MA and further enhanced by rapamycin.</p><p><strong>Conclusions: </strong>3D spheroid culture substantially augments the therapeutic efficacy of UC-MSCs by boosting autophagy and suppressing NLRP3 inflammasome signaling, resulting in enhanced protection of RPE cells from oxidative and inflammatory injury. These findings provide preclinical evidence supporting 3D MSCs as a promising therapeutic strategy for AMD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820688","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":"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":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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 &lt; 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 &lt; 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 &lt; 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;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}