Stem Cells Translational Medicine最新文献

{"title":"Whole-genome CRISPR screening identifies genetic modifiers of stem cell-derived islet transplantation.","authors":"Marlie M Maestas, Kameron Bradley, Mira Shunkarova, Noyonika Mukherjee, Matthew Ishahak, James Lu, Jeffrey R Millman","doi":"10.1093/stcltm/szag012","DOIUrl":"10.1093/stcltm/szag012","url":null,"abstract":"<p><strong>Introduction: </strong>Genetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy; however, genetic perturbations that modulate transplantation outcomes have yet to be systematically explored.</p><p><strong>Methods: </strong>To identify potential targets, we performed an unbiased whole-genome CRISPR-activation screen in transplanted stem cell-derived islets (SC-islets). Specifically, we created a stem cell line with CRISPR-activation components (HUES8-VPR) and then transduced these stem cells with a lentiviral guide RNA library targeting the whole human genome. Following transduction, the stem cells were differentiated into SC-islets, which were subsequently transplanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice. After transplantation, SC-islets were extracted for next-generation sequencing.</p><p><strong>Results: </strong>The screen identified multiple candidates, including the Fc alpha/mu receptor (FCAMR). In vitro characterization revealed that FCAMR overexpression did not negatively affect SC-islet function or transcriptomic identity. Mice subcutaneously transplanted with SC-islets overexpressing FCAMR had reduced blood glucose levels and increased C-peptide compared to controls. Additionally, mice receiving FCAMR-modified grafts into the kidney capsule or hindleg muscle maintained a higher body weight compared to controls in a diabetic setting.</p><p><strong>Conclusions: </strong>In conclusion, this study demonstrats improved glucose regulation at a subcutaneous transplant site. In addition, we show that FCAMR SC-islets could play a role in systemic metabolism when transplanted into the kidney capsule or hindleg muscle. Overall, our study establishes a functional screening approach to identify gene candidates to improve SC-islet transplantation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522022","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":"Apoptotic periodontal ligament stem cells combined with developmental endothelial locus-1 counteract experimental periodontitis with type 2 diabetes mellitus.","authors":"Qian Ma, Houxuan Li, Xiaoyu Yang, He Wang, Yiyao Hu, Han Li, Deping Zeng, Jie Li, Jinlin Song","doi":"10.1093/stcltm/szag014","DOIUrl":"10.1093/stcltm/szag014","url":null,"abstract":"<p><p>Stem cell therapy has been utilized in the treatment of periodontitis. Recent studies have demonstrated that treatment with apoptotic mesenchymal stem cells (MSCs) exhibits immunomodulatory effects comparable to those of living MSCs. However, the effect of type 2 diabetes mellitus (T2DM) on the efficacy of apoptotic MSCs therapy for periodontitis remains poorly understood. In this study, a ligature-induced experimental periodontitis model was established in wild-type (WT) and db/db mice, followed by the injection of exogenous apoptotic periodontal ligament stem cells (PDLSCs). The results revealed suboptimal therapeutic outcomes with apoptotic PDLSCs in db/db mice. It was observed that the progression of periodontitis was associated with a reduction in the expression of developmental endothelial locus-1 (DEL-1) in experimental periodontitis model. Additionally, the expression of DEL-1 was partially restored during the resolution phase of inflammation. T2DM mice exhibited exacerbated alveolar bone loss and suppressed regeneration, accompanied by the inhibition of DEL-1 expression. In co-culture experiments, impaired macrophage efferocytosis of apoptotic PDLSCs was ameliorated by the addition of exogenous DEL-1 under lipopolysaccharide and high glucose conditions. Moreover, the co-administration of exogenous DEL-1 enhanced the therapeutic efficacy of exogenous apoptotic PDLSCs in db/db mice. In conclusion, diminished DEL-1 expression and impaired macrophage efferocytosis constrain the therapeutic potential of exogenous apoptotic PDLSCs in periodontitis with T2DM. The diminished therapeutic efficacy may be alleviated by the combination of exogenous DEL-1 and apoptotic PDLSCs, offering novel insights into potential therapeutic strategies for periodontitis with T2DM.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522019","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":"Bone tissue regeneration: role of osteocyte mechanosensing and mechanotransduction.","authors":"Hadi Seddiqi, Jenneke Klein-Nulend, Jianfeng Jin","doi":"10.1093/stcltm/szag017","DOIUrl":"10.1093/stcltm/szag017","url":null,"abstract":"<p><p>Critical-sized bone defects caused by trauma, tumor resection, injury, and/or surgical intervention are posing significant clinical challenges. Bone tissue regeneration is crucial for restoring critical-sized bone defects. Central to the bone regenerative capability is the dynamic interplay between bone cells, particularly osteocytes, which are the most abundant and long-lived bone cells, functioning as key mechanosensors in bone. Osteocytes detect mechanical stimuli, for example, fluid shear stress, compressive or tensile strain, and hydrostatic pressure, and convert these into biochemical signals through mechanotransduction. The biochemical signals (eg, calcium ions, Wnt, etc.) regulate osteoblast and osteoclast-mediated remodeling. Osteocytes communicate with osteoblasts and osteoclasts via paracrine factors, including nitric oxide, prostaglandins, and sclerostin. Moreover, estrogen deficiency is known to alter osteocyte mechanosensitivity, impair osteocyte signaling, and dysregulate bone remodeling. Understanding how mechanical and hormonal factors affect osteocyte signaling is essential for developing effective therapeutic interventions. This concise review explores the role of osteocyte mechanosensing and mechanotransduction in bone tissue regeneration to improve bone healing, especially in critical-sized bone defects. The cellular and molecular mechanisms underlying bone regeneration and remodeling are discussed, including the role of stem cells in bone regeneration, that is, osteogenic differentiation potential and secretion of bioactive factors that promote new bone formation and vascularization. Finally, we explore the translational and clinical implications of osteocyte mechanobiology, discussing current challenges and potential advancements in bone tissue engineering and regenerative medicine. By integrating fundamental mechanobiological principles with clinical strategies, this concise review highlights the clinical potential of modulating osteocyte behavior for improved bone regeneration.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692171","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":"METTL1-deficient mesenchymal stem cells protect against metabolic-associated fatty liver disease by increasing NAMPT secretion.","authors":"Jiang Du, Yuxuan Zhang, Chiheng Wang, Yuyuan Wang, Hongen Zhang, Dunyong Zhao, Juntang Lin","doi":"10.1093/stcltm/szag016","DOIUrl":"10.1093/stcltm/szag016","url":null,"abstract":"<p><strong>Background: </strong>Genetically modified mesenchymal stem cells (MSCs) have been shown to enhance their therapeutic properties, offering more effective treatment options for various diseases, including metabolic associated fatty liver disease (MASLD). The m7G methyltransferase METTL1 plays a critical role in regulating RNA splicing, stability, and translation. This study presents our findings on METTL1 modified human umbilical cord MSCs, emphasizing their therapeutic effects and the mechanisms involved in treating MASLD.</p><p><strong>Methods: </strong>METTL1 knockdown MSCs were generated via lentiviral shRNA. Key characteristics, including senescence, proliferation, cell cycle, and apoptosis, were assessed in vitro. A high-fat diet (HFD)-induced MASLD mouse model was used to evaluate the effects of MSC transplantation through serological, biochemical, and pathological analyses. Molecular mechanisms were explored using immunofluorescence (IF), Western blotting (WB), and quantitative PCR (qPCR).</p><p><strong>Results: </strong>Our results indicate that METTL1-deficient MSCs exhibit reduced proliferative capacity and increased susceptibility to senescence and apoptosis. Remarkably, these MSCs significantly decreased lipid accumulation in both in vitro and in vivo MASLD models. We found that METTL1-deficient MSCs secrete higher levels of NAMPT, which activates SIRT1, leading to the inhibition of SREBP1-mediated lipogenic genes. Inhibition of NAMPT reversed the protective effects of METTL1-deficient MSCs against MASLD-related lipid metabolic disorders. Furthermore, overexpression of METTL1 in MSCs exacerbated lipid metabolic disorders in MASLD mice by inhibiting the NAMPT/SIRT1/SREBP1 signaling pathway.</p><p><strong>Conclusion: </strong>METTL1-deficient MSCs alleviate MASLD-associated lipid metabolic disorders via NAMPT secretion. This suggests that genetically modified MSCs targeting METTL1 may represent a promising therapeutic strategy for the treatment of MASLD.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575486","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":"Senescence profiling and biomarker identification in cell product based on adipose tissue-derived mesenchymal stromal cells.","authors":"Ellen Mønsted Johansen, Cecilie Hoeeg, Rebekka Harary Søndergaard, Lisbeth Drozd Højgaard, Laura Lykke Lethager, Stine Bangsgaard, Jens Kastrup, Tu Hu, Thomas Litman, Morten Juhl Nørgaard","doi":"10.1093/stcltm/szag011","DOIUrl":"10.1093/stcltm/szag011","url":null,"abstract":"<p><strong>Background/aim: </strong>Adipose tissue-derived mesenchymal stromal cells (ASC) are used in advanced therapy medicinal products due to their regenerative and immunomodulatory properties. Increasing the number of dosages derived from each donor product is essential to reduce variability and improve scalability of cell therapy. However, extended in vitro expansion may induce cellular senescence, potentially compromising therapeutic efficacy. This study aimed to assess the remaining proliferative potential of a cryopreserved ASC product and identify robust transcriptomic -biomarkers of senescence.</p><p><strong>Methods: </strong>ASC from five donors were cultured until replicative senescence or passage 10. Morphology, growth kinetics, and confluence were monitored. Bulk RNA sequencing was performed on samples from passage 1, 3, 6, and final passage. Principal component analysis, differential expression, gene set variation analysis, and variance partitioning were used to characterize transcriptional changes and identify biomarkers.</p><p><strong>Results: </strong>ASC maintained stable proliferation and morphology for at least three passages post-thaw. Major transcriptional shifts occurred between passage 3 and later passages. Senescence-associated gene enrichment increased progressively, with donor-specific variation evident at intermediate passages. Forty biomarkers (20 upregulated, 20 downregulated) were identified with expression changes primarily attributable to passage rather than donor identity.</p><p><strong>Conclusion: </strong>Cryopreserved ASC retain substantial proliferative capacity post-thaw. Senescence develops gradually and is detectable through consistent transcriptomic changes. These findings relate to proliferative and senescence-associated molecular changes and do not directly assess therapeutic efficacy. The identified biomarkers provide a foundation for developing senescence-focused quality control assays to support safe and effective ASC-based therapies.Significance statementThis study identifies promising biomarker candidates for developing a quality control assay to detect cellular senescence and evaluates the remaining replicative potential of a GMP-approved investigational medicinal product. These findings contribute to improving the safety and consistency of cell-based therapies by enabling detection of senescence-related changes.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370417","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":"MSC-small extracellular vesicles alleviated Th2-airway inflammation by regulating the metabolism of DCs in mice.","authors":"Long-Xin Huang, Lifen Wen, Tian Tian, Zi-Cong Wu, Chan-Gu Li, Qi- Sun, Ying-Chun Xie, Xiao-Qing Liu, Zhi-Rou Zhou, Zhi-Bin Xu, Bi-Xin He, Qing-Ling Fu","doi":"10.1093/stcltm/szag010","DOIUrl":"10.1093/stcltm/szag010","url":null,"abstract":"<p><strong>Background: </strong>Allergic airway inflammation is one of the chronic inflammatory diseases and is generally dominated by T helper 2 cells (Th2). Dendritic cells (DCs) are essential to mounting the Th2-mediated airway inflammation by presenting inhaled antigens to prime CD4+ T cells. Small extracellular vesicles (sEV) derived from mesenchymal stem cells (MSCs) exhibited great interest in intractable diseases. However, the effects and mechanisms of MSC-sEV on DCs in airway inflammation is still unclear.</p><p><strong>Methods: </strong>We isolated MSC-sEV using anion-exchange chromatography. Mouse bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs (moDCs) were used to study the effects of MSC-sEV on dendritic cell surface molecules and their cytokine release. Mice were sensitized with house dust mites (HDM) to induce airway inflammation, and treated with MSC-sEV, the effects of sEV on murine DCs were identified. Extracellular flux analysis techniques were used to study the effects of MSC-sEV on the metabolic state of dendritic cells. RNA sequencing to study altered gene expression in BMDCs after MSC-sEV treatment.</p><p><strong>Results: </strong>MSC-sEV mitigated the accumulation of Th2-associated cDC2s and moDCs in mouse lung in response to HDM. In vitro, MSC-sEV treatment significantly attenuated the activation of BMDCs. Furthermore, we identified that DCs were able to take MSC-sEV in vitro and in vivo. Mechanistically, MSC-sEV exerted regulatory effects on the metabolic pathways of murine DCs, specifically enhancing the reliance on oxidative phosphorylation of BMDCs. Importantly, MSC-sEV displayed similar effects on human moDCs.</p><p><strong>Conclusions: </strong>MSC-sEV are able to alter the metabolic state of DCs, favoring DCs to maintain OXPHOS (oxidative phosphorylation) rather than glycolysis, thereby reducing DCs-initiated inflammatory responses and attenuating Th2 lung inflammation, suggesting MSC-sEV can be a potential clinical therapy for airway inflammation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310553","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":"Adamts4 coordinates the transcriptomic profile of primary rat costal chondrocytes.","authors":"Zhenxing Wei, Yijie Chen, Wanyi Kou, Yifan Zhang, Wenqi Sha, Ruixin Guo, Yuran Lei, Ningrui Zhang, Yanxia Shi, Zhenghui Wang","doi":"10.1093/stcltm/szag004","DOIUrl":"10.1093/stcltm/szag004","url":null,"abstract":"<p><p>Chondrocytes play a pivotal role in cartilage tissue engineering. ADAMTS4 gene encodes aggrecanase-1, which is known to affect chondrocyte biology by regulating aggrecan degradation. However, the molecular mechanism by which ADAMTS4 regulates chondrocyte phenotype remains unclear. To comprehensively investigate Adamts4-regulated genes in primary rat costal chondrocytes, we conducted siRNA-mediated Adamts4 knockdown alongside RNA sequencing (RNA-seq), co-immunoprecipitation coupled with mass spectrometry (CO-IP/MS), and enhanced RNA immunoprecipitation sequencing (iRIP-seq). Our results demonstrated that Adamts4 knockdown did not affect chondrocyte apoptosis. However, Adamts4 silencing markedly changed the expression levels of numerous genes linked to cell differentiation and cell cycle progression. CO-IP/MS experiments showed that Adamts4 extensively interacted with RNA-binding proteins (RBPs) in rat chondrocytes. iRIP-seq data suggested that Adamts4 bound to a large number of transcripts, especially those with AU-rich motifs at coding regions. Most interestingly, we found three genes Hmox1, Acan, and Col2a1, which were deregulated upon Adamts4 silencing and enriched in the Adamts4 RIP samples. Altogether, these results indicate that Adamts4 knockdown remarkably modulates the transcriptomic profile of rat chondrocytes. Interactions with RBPs or target mRNAs might contribute to Adamts4-mediated alterations in gene expression. These findings warrant further investigation of the crucial target genes of ADAMTS4 in the regulation of human chondrocyte behaviors.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285046","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":"FGF2 alters the calvarial suture niche homeostasis shifting skeletal stem cell/progenitors toward an osteo-angiogenic coupling fate.","authors":"Natalina Quarto, Siddharth Menon, Jason L Guo, Ankit Salhotra, Michael T Longaker","doi":"10.1093/stcltm/szag003","DOIUrl":"10.1093/stcltm/szag003","url":null,"abstract":"<p><p>Calvarial sutures, the major growth centers for skull morphogenesis, are currently regarded as \"niches\" for calvarial stem cells. Our previous study has identified a skeletal stem/progenitor cell population resident within the suture mesenchyme. Moreover, we have shown that decrease and/or imbalance of their representation in the \"niche\" impact the fate of a non-fusing suture to fusing-suture and vice versa. Herein, taking advantage of an our established ex vivo calvarial suture explant model we investigated the impact triggered by FGF2, a pro-osteogenic and pro-angiogenic factor, on our skeletal stem/progenitor cell population resident in the suture mesenchyme. Multi-omics data integration combined with cell biology identifies dynamic changes in the representation of skeletal stem/progenitor cell population thus, unveiling within them functionally distinct populations with angiogenesis-competent properties. Findings altogether indicate that FGF2 stimuli may alter the suture \"niche\" homeostasis and that coordinate an osteogenesis-angiogenesis coupling within skeletal stem/progenitor cell sub-populations.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285112","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":"Towards evolutionary guided precision medicine of acute myeloid leukemia and Fanconi anemia associated bone marrow failure.","authors":"Robert A Beckman, Pamela S Becker, Julia Gallini, Gary M Kupfer, Alvin P Makohon-Moore, Matthew D McCoy, Oleksandr Sverdlov","doi":"10.1093/stcltm/szag008","DOIUrl":"10.1093/stcltm/szag008","url":null,"abstract":"<p><p>Carcinogenesis and acquisition of multidrug resistance within established cancers are both multistep evolutionary processes in which stem cells play a role. This perspective will briefly review two corresponding theoretical constructs under development. Efficiency of carcinogenesis (EOC) considers multistep carcinogenesis and predicts the effect of differing dynamics on the efficiency of generating a transformed founder cell. EOC has been applied to evaluation of the role of genetic instability in carcinogenesis. Dynamic precision medicine (DPM) is a method for providing personalized treatment sequences for cancer while explicitly considering intracancer subclonal heterogeneity and evolutionary dynamics (growth and evolutionary rates). It adapts therapy frequently and proactively by anticipating the kinetics of multidrug resistance prior to its detection, and prioritizing its prevention. Simulations suggest potential to substantially increase survival and cure rates across a broad range of clinical presentations. Both of these problems implicate very small subclones within stem cell and/or differentiated compartments, and evolution may occur over months to years. We describe novel experimental technologies for quantifying longitudinal dynamics of very large numbers of cells for prolonged periods, allowing detection and tracking of rare events and their evolution over time. We further highlight two potential applications. In Fanconi anemia, optimal treatment sequences for minimizing bone marrow failure while not increasing the risk of leukemia may be designed using EOC and DPM and tested in laboratory models. In refractory acute myeloid leukemia, high throughput molecular characterization and drug sensitivity screening of subclones is showing clinical promise, and may be further optimized with DPM.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435659","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":"Corneal regenerative contribution of endogenous and grafted limbal-corneal cells in a mouse model of simple limbal-corneal epithelial transplantation.","authors":"Marcia F D Costa, Nicola Piazza, Erika Bonacci, Sissi Dolci, Francesca Ciarpella, Marzia Di Chio, Stefania Zorzin, Andrea Corsi, Alessandro Piva, Cristiano Chiamulera, Zulkifal Malik, Riccardo Esposito, Francesco Bifari, Stefano Ugel, Adriano Fasolo, Antonella Motta, Stefano Ferrari, Emilio Pedrotti, Ilaria Decimo","doi":"10.1093/stcltm/szag007","DOIUrl":"10.1093/stcltm/szag007","url":null,"abstract":"<p><p>Severe ocular damage, such as corneal alkali-injury, can compromise the limbal stem cell (LSC) niches, leading to LSC deficiency (LSCD) and resulting in significant vision impairment. Current insights into the wound healing process associated with simple limbal epithelial transplantation (SLET), a therapeutic intervention for LSCD, are derived solely from clinical studies, which impose methodological limitations and hinder a complete understanding of the cellular dynamics underlying SLET. For the first time, we adapted the clinical SLET procedure to a mouse model of LSCD, enabling a robust and detailed assessment of short- and long-term morphological, immunomodulatory and cell-fate outcomes in corneal regeneration. We demonstrated that simple limbal-corneal epithelial transplantation (SLCET) treatment effectively reduces corneal opacification, vascularization, and inflammation induced by alkali-injury, with persistent benefits. We used transgenic GFP-expressing mice to isolate GFP-positive limbal-corneal cells and trace their fate in the context of SLCET. Our results revealed that both endogenous and transplanted cells contribute to replenishing the depleted limbal-corneal cell population. Furthermore, we showed that the engrafted-cells retained a long-term proliferative capacity and stemness phenotype, underscoring their role in sustained corneal regeneration. Overall, our study provides a temporal and mechanistic overview of SLCET outcomes, highlighting the engrafted-cells as key players in corneal regeneration. This framework also holds a strong translational potential for enhancing SLET's efficacy and uncovering novel LSC modulators.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318222","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}