Stem Cells Translational Medicine最新文献

{"title":"Artificial intelligence and systems biology analysis in stem cell research and therapeutics development.","authors":"Thayna Silva-Sousa, Júlia Nakanishi Usuda, Nada Al-Arawe, Irene Hinterseher, Rusan Catar, Christian Luecht, Pedro Vallecillo Garcia, Katarina Riesner, Alexander Hackel, Lena F Schimke, Haroldo Dutra Dias, Igor Salerno Filgueiras, Helder I Nakaya, Niels Olsen Saraiva Camara, Stefan Fischer, Gabriela Riemekasten, Olle Ringdén, Olaf Penack, Tobias Winkler, Georg Duda, Dennyson Leandro M Fonseca, Otávio Cabral-Marques, Guido Moll","doi":"10.1093/stcltm/szaf037","DOIUrl":"10.1093/stcltm/szaf037","url":null,"abstract":"<p><strong>Background: </strong>Stem cell research has rapidly advanced during the past decades, but the translation into approved clinical products is still lagging behind. Multiple barriers to effective clinical translation exist. We hypothesize that an ineffective use of the existing wealth of data from both product development and clinical trials is a crucial barrier that hampers effective clinical implementation of stem cell therapies.</p><p><strong>Methods and results: </strong>Here, we summarize the contribution of systems biology (SysBio) and artificial intelligence (AI) in stem cell research and therapy development, to better understand and overcome these barriers to effective clinical translation. Advancements in cell product profiling technology, clinical trial design, and adjunct clinical monitoring, offer new opportunities for a more integrated understanding of both, product and patient performance. Synergy of SysBioAI analysis is boosting a more rapid, integrated, and informative analysis of large‑scale multi‑omics data sets of patient and clinical trial outcomes, thus enabling the \"Iterative Circle of Refined Clinical Translation\". This SysBioAI‑supported concept can assist more effective development and clinical use of stem cell therapeutics through iterative adaptation cycles. This includes product‑ and patient‑centered clinical safety and efficacy/potency evaluation through paired identification of suitable biomarkers of clinical response.</p><p><strong>Conclusion: </strong>Integrated SysBioAI-use is a powerful tool to optimize the design and outcomes of clinical trials by identifying patient-specific responses, contributing to enhanced treatment safety and efficacy, and to spur new patient-centric and adaptable next-generation deep-medicine approaches.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186791","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":"Hematopoietic stem cell therapy with gene modification to treat sickle cell disease.","authors":"Julia Ball, Avery Bradley, Anh Le, John F Tisdale, Naoya Uchida","doi":"10.1093/stcltm/szaf042","DOIUrl":"10.1093/stcltm/szaf042","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) reconstitute blood cells throughout life. DNA-level correction of HSCs allows for a one-time cure of genetic diseases, including sickle cell disease (SCD). Sickle cell disease is one of the most common single-gene disorders; therefore, SCD is a prime candidate for gene therapy. Several drug therapies are available for SCD, including hydroxyurea, which is the first-line choice despite requiring lifelong administration. Allogeneic HSC transplantation is a one-time, curative treatment for SCD with limited availability of histocompatible donors. Therefore, autologous HSC gene therapy was developed using patients' own HSCs with lentiviral gene addition/silencing and clustered regularly interspaced short palindromic repeats gene editing, making gene therapy applicable to most patients. However, the established method of HSC gene therapy requires costly and complex ex vivo HSC culture. Therefore, in vivo HSC gene therapy is being developed to treat SCD, envisioning a single-injection HSC-targeted gene delivery system. This review discusses various therapeutic methods to treat SCD, the development of HSC gene therapy, and clinical gene therapy trials in SCD, ranging from FDA-approved to novel in vivo gene therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087159","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":"Distal lung organoids derived from adult stem cells as novel tools in deciphering mechanisms of lung regeneration, infection, and cancer.","authors":"Mark Bell, Anna D Krasnodembskaya","doi":"10.1093/stcltm/szaf040","DOIUrl":"10.1093/stcltm/szaf040","url":null,"abstract":"<p><p>While lung research has made great strides in understanding lung physiology, lung pathology still presents a major burden to patients and healthcare systems globally. To develop new effective therapeutics to improve lung regeneration, prevent spread of infections, or treat lung cancers, obscured fundamental processes of the lung must be dissected. Current understanding of lung cell cross talk has been limited due to a lack of accessible and representative models. Since the COVID-19 pandemic, many new foundational methodologies for distal organoid formation have been published, which eliminate difficulty in distal organoid longevity and donor cell extraction efficiency. This review describes how recent advances within distal lung organoid technology have been used to investigate lung regeneration, fibrosis, infection trafficking, personalized medicine, and mechanism of chronic lung pathology using donor cells. Additionally, the applicability of distal lung organoids to investigation of the roles of endothelium and previously unknown distal epithelial and mesenchymal cell populations is discussed. Finally, new techniques and methods for tackling current challenges within the field, such as integration of immune cells and vascularization of organoids are highlighted. This overview will therefore illustrate the potential of distal lung organoids to be tissue representative models, which will be crucial for evolving scientific knowledge of lung physiology.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087084","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":"Metabolic regulation in the senescence process of stem cells.","authors":"YingYing Wei, Bin Zhang, Qingli Bie, Baoyu He","doi":"10.1093/stcltm/szaf041","DOIUrl":"10.1093/stcltm/szaf041","url":null,"abstract":"<p><strong>Background: </strong>Aging is an inevitable and complex biological process characterized by progressive cellular and functional deterioration, leading to increased disease susceptibility and mortality. Stem cells, endowed with unique self-renewal and multipotent differentiation capabilities, play a pivotal role in tissue homeostasis and regenerative processes. However, the aging process triggers stem cell senescence, manifested by diminished proliferative capacity and differentiation potential, ultimately compromising tissue regeneration and contributing to the pathogenesis of various age-related disorders, including neurodegeneration, cardiovascular diseases, and metabolic syndromes.</p><p><strong>Main findings: </strong>Metabolic plasticity serves as a fundamental mechanism enabling stem cells to dynamically adapt their energy requirements during self-renewal and lineage commitment. Emerging evidence indicates that cellular metabolism extends beyond its conventional role in energy production, actively participating in the regulation of stem cell fate decisions. Notably, nutrient-sensitive metabolites constitute a sophisticated metabolism-epigenetic axis that integrates metabolic flux, signaling pathways, and epigenetic modifications to precisely orchestrate cellular behavior. This regulatory axis is indispensable for maintaining tissue homeostasis and facilitating regeneration, thereby positioning metabolic reprogramming as a promising therapeutic strategy for mitigating aging-associated decline.</p><p><strong>Conclusions: </strong>In conclusion, elucidating the intricate crosstalk between stem cell metabolism and the aging process unveils novel opportunities for developing innovative anti-aging interventions and enhancing tissue repair. Future investigations should focus on the precise manipulation of metabolic pathways to effectively counteract age-related functional deterioration and promote longevity.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092500","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":"Microencapsulated 3D culture of human umbilical cord-derived mesenchymal stem cells enhances their therapeutic effect on intrauterine adhesion.","authors":"Hongjiang Liu, Xiaohua Jiang, Jin Qian, Xuan Xu, Shujun Yu, Zhongqin Tang, Ying Wang, Qiong Xing, Heng Tang, Jianye Wang, Zhaolian Wei","doi":"10.1093/stcltm/szaf044","DOIUrl":"10.1093/stcltm/szaf044","url":null,"abstract":"<p><p>Therapeutic application of mesenchymal stem cells is emerging as a potential strategy for the management of intrauterine adhesion (IUA). However, conventional 2D cultures often face issues such as insufficient cell quantities and suboptimal efficacy. In this study, we investigated the potential of microencapsulated 3D culture in enhancing the proliferation and stemness of human umbilical cord-derived mesenchymal stem cells (hUCMSCs), and their potential augmentation for antifibrotic treatment of IUA via the transforming growth factor beta 1 (TGF-β1)/Smad3 signaling pathway. Here, hUCMSCs were encapsulated in sodium alginate shells, and the microencapsulated 3D culture of hUCMSCs (3D-hUCMSCs) was harvested after removal of the encapsulation. We assessed the amount, cell proliferation, and the stemness gene expression of 3D-hUCMSCs and 2D cultured hUCMSCs. Subsequently, the therapeutic effect of 3D-hUCMSCs was evaluated by specific staining and mating experiments in the IUA mouse model. The expression of the TGF-β1/Smad3 signaling pathway was analyzed by western blot and quantitative real-time polymerase chain reaction. Our results showed that microencapsulated 3D culture significantly enhanced cell proliferation and elevated stemness gene expression, compared to traditional 2D culture. Furthermore, the endometrial thickness and number of glands increased, and the endometrial fibrosis and inflammation ameliorated in 3D-hUCMSCs administration. Moreover, 3D-hUCMSCs significantly inhibited the expression of the TGF-β1/Smad3 signaling pathway and restored the fertility. These findings indicate that microencapsulated 3D culture enhances cell proliferation and stemness of hUCMSCs. The 3D-hUCMSCs improved the endometrial recovery in structure and function. Microencapsulated 3D culture promoted the antifibrotic and anti-inflammatory effects of hUCMSCs in the treatment of IUA. This study introduces a novel strategy of microencapsulated 3D-hUCMSCs for IUA treatment.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131992","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":"Rapid manufacturing of angiogenic cellular collagen patches for ischemic cardiomyopathy.","authors":"Eric Pfrender, Sungwoo Kim, John A Farag, Shin Yajima, Yujiro Kawai, Koji Kawago, Umayr Syed, Gentaro Ikeda, Tsuyoshi Ueyama, Hiroyuki Takashima, Alex Dalal, Yuanjia Zhu, Kenzo Ichimura, Yu Liu, Seyedsina Moeinzadeh, Jayme Koltsov, Joseph C Wu, Y Joseph Woo, Phillip C Yang, Yunzhi P Yang, Yasuhiro Shudo","doi":"10.1093/stcltm/szaf035","DOIUrl":"10.1093/stcltm/szaf035","url":null,"abstract":"<p><strong>Background: </strong>One in ten Americans carry a lifetime risk of ischemic heart failure, the most severe form of ischemic heart disease. Carrying a nearly 50% five‑year mortality rate, no interventional therapy exists to treat the underlying cause, microvascular malperfusion. In efforts to combat microvascular malperfusion, our group has utilized synergistic application of endothelial progenitor cells (EPCs) and smooth muscle cells (SMCs) to induce angiogenesis in ischemic myocardium.</p><p><strong>Methods: </strong>Cells are then embedded into a rapidly manufacturable compressed collagen (CC) patch to provide a biosimilar scaffold ready for transplantation. The performance of the cellular compressed collagen patch was then tested on a rodent acute myocardial infarction model of ischemic heart failure.</p><p><strong>Results: </strong>By post‑transplantation Day 28, the cellular CC patch improved left ventricular ejection fraction when compared to an acellular CC patch and control (cellular: 49.1 ± 1.8%; acellular: 38.0 ± 2.6%; control: 39.2 ± 2.1%; ANOVA P = .0006). Cellular CC patch transplantation also induced mature angiogenesis as shown by arteriolar density (cellular: 1084 ± 98 αSMA+vWF+/mm2; acellular: 338 ± 57 αSMA+vWF+/mm2; control: 449 ± 39 αSMA+vWF+/mm2; ANOVA P = .0003) and vascular maturation index (cellular: 0.67 ± 0.04; acellular: 0.48 ± 0.02; and control: 0.46 ± 0.04, P = .001).</p><p><strong>Conclusions: </strong>In conclusion, transplantation of a rapidly manufacturable EPC‑SMC‑based compressed collagen patch effectively rescues myocardial function by enhancing neovascularization and attenuating post‑infarction myocardial injury.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092443","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":"Preclinical efficacy of adipose-derived cell therapies for the treatment of myositis.","authors":"Baptiste Pileyre, Silvia Gandolfi, Catalina Abad, Thara Jaworski, Laurent Drouot, Laetitia Jean, Olivier Boyer, Isabelle Dubus, Jérémie Martinet","doi":"10.1093/stcltm/szaf038","DOIUrl":"10.1093/stcltm/szaf038","url":null,"abstract":"<p><strong>Importance: </strong>Idiopathic inflammatory myopathies, commonly referred as myositis, are autoimmune diseases that cause muscle damage, progressive weakness, and disability. Current treatments, including corticosteroids and immunosuppressants, have significant limitations, highlighting the need for new therapies.</p><p><strong>Objective: </strong>This preclinical study explored the therapeutic potential of adipose tissue-derived cell therapies, specifically stromal vascular fraction (SVF) and adipose-derived stem cells (ADSC), using an Icos-/- NOD mouse model of spontaneous myositis.</p><p><strong>Design: </strong>SVF and ADSC were extracted from CD1 female mice adipose tissue and cultured. Various doses were injected intramuscularly into the right hind limb of 20- to 22-week-old female Icos-/- NOD mice with a control group. The therapeutic effects were assessed through clinical scoring, grip strength test, and motor function analysis using Catwalk system. Muscle atrophy was evidenced by histology, and systemic inflammation was analyzed by flow cytometry.</p><p><strong>Results: </strong>Mice treated with either SVF or ADSC showed a dose-dependent slowdown in disease progression and improvements in motor functions, such as gait, movement, speed, and weight distribution between the legs. Histological analysis showed a reduction in muscular atrophy, particularly in the injected limb. Flow cytometry analysis on lymph nodes showed shifts in leukocyte populations, with reduced expression of inflammatory and activation markers.</p><p><strong>Conclusions and relevance: </strong>Overall, this study demonstrated the therapeutic potential intramuscular injection of SVF or ADSC in the Icos-/- NOD mouse model of myositis, providing a proof-of-concept for the use of adipose tissue-derived cell therapies in the treatment of idiopathic inflammatory myopathies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087107","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":"Anti-tumor effect of intratumoral administration of induced pluripotent stem cell-derived NKT cells on glioblastoma through CD155/DNAM-1 interaction.","authors":"Ko Ozaki, Takahiro Aoki, Masayoshi Kobayashi, Mariko Takami, Midori Kobayashi, Toshihiro Ito, Keita Ogawa, Hidekazu Tanaka, Kai Nishii, Katsuhiro Nishimura, Kiwamu Motoyoshi, Iori Kojima, Daisuke Katsumi, Daiki Shimizu, Hongxuan Wang, Motoko Yagi Kimura, Kiyoshi Hirahara, Haruhiko Koseki, Yoshinori Higuchi, Shinichiro Motohashi","doi":"10.1093/stcltm/szaf036","DOIUrl":"10.1093/stcltm/szaf036","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the most malignant brain tumor with the poorest prognosis, but there have been no significant therapeutic advances in the past 20 years. Intratumoral administration of invariant natural killer T (iNKT) cells for glioblastoma has recently been reported and is promising immunotherapy. However, the low presence of iNKT cells in peripheral blood made it difficult to use iNKT cells as adoptive immunotherapy. Therefore, we used induced pluripotent stem cell-derived NKT (iPS-NKT) cells and analyzed their anti-tumor effect.</p><p><strong>Methods: </strong>Induced pluripotent stem cell-derived NKT cells were generated by the previously reported protocol. The anti-tumor effect of iPS-NKT cells was confirmed against several glioblastoma cell lines. We also analyzed the expression of natural killer cell receptors of iPS-NKT cells and ligands of glioblastoma cell lines to know which interactions are dominant. In vivo, using an orthotopic glioblastoma mouse model, we compared the survival and tumor volume in mice iPS-NKT cells administered intratumorally with those in mice of no treatment group.</p><p><strong>Results: </strong>We demonstrated that iPS-NKT cells have anti-tumor effects even in glioma cell lines with low CD1d expression and that CD155/DNAM-1 interactions are associated with these anti-tumor effects. In the orthotopic low CD1d-expressing glioblastoma mouse model, iPS-NKT-treated mice showed markedly prolonged survival and suppressed tumor volume.</p><p><strong>Conclusion: </strong>We confirmed the anti-tumor effects of iPS-NKT cells on glioblastoma cells in vitro and in vivo. The anti-tumor activity was suggested to be mainly due to the interaction between CD155 and DNAM-1. Intratumoral administration of iPS-NKT cells has potential anti-tumor effects on glioblastoma in the clinic.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087329","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":"Mesenchymal progenitor-derived proteoglycan 4 regulates the transdifferentiation of chondrocytes into osteoblasts during fracture healing.","authors":"Nicoletta Ninkovic, Jessica May Corpuz, Alana Stahl, Alexandra Olsen, Colton M Unger, Aria Ahadzadeh Ardebili, Haochen Sun, Juyeon Cha, Daphne Kaketsis, Sarah L Manske, Ifaz T Haider, Ralph S Marcucio, Tannin A Schmidt, Gregory D Jay, T Michael Underhill, W Brent Edwards, Derrick E Rancourt, Jeff Biernaskie, Roman J Krawetz","doi":"10.1093/stcltm/szaf043","DOIUrl":"10.1093/stcltm/szaf043","url":null,"abstract":"<p><strong>Introduction: </strong>Proteoglycan 4 (PRG4), also known as lubricin, is essential for maintaining tissue homeostasis and acts as a lubricant that protects joint surfaces from wear and tear. Our previous studies have demonstrated that PRG4 plays multiple roles in wound healing in mice and pigs. Specifically, PRG4 derived from Hic1+ mesenchymal progenitor cells (MPCs) is crucial for maintaining tissue homeostasis in the dura mater near the spinal cord, and in the skin it contributes to ear wound healing in mice. Additionally, mice lacking PRG4 exhibit abnormal bone structure and function. However, the role of PRG4 in fracture healing remains unclear.</p><p><strong>Methods: </strong>To investigate the role of PRG4 in fracture repair, we generated mice with a conditional deletion of Prg4 in the Hic1+ lineage. The presence and contribution of Hic1+ progenitors at the fracture site were assessed at 2‑ and 4‑weeks post‑injury (wpi). Bone healing quality was evaluated, and the cellular phenotype within the fracture callus was examined.</p><p><strong>Results: </strong>We observed Hic1+ progenitors at the fracture site at both 2‑ and 4‑wpi. Conditional deletion of Prg4 in these progenitors impaired the quality of new bone formation at the fracture site. Furthermore, PRG4 was required to maintain the cartilaginous phenotype of callus cells. In its absence, chondrocytes underwent premature transformation into osteoblasts, disrupting the normal progression of fracture healing.</p><p><strong>Discussion: </strong>These findings provide new insights into the role of PRG4 in bone regeneration. PRG4, derived from Hic1+ MPCs, is critical for regulating the balance between chondrogenesis and osteogenesis during fracture repair. By preventing premature chondrocyte‑to‑osteoblast transition, PRG4 supports proper callus formation and bone healing. This work highlights the importance of PRG4 and Hic1+ MPCs in fracture repair and extends their known functions in tissue homeostasis and wound healing.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092439","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":"Modeling rare genetic disease with patient-derived induced pluripotent stem cells: reassessment of the minimum numbers of lines needed.","authors":"Ashok R Dinasarapu, Diane J Sutcliffe, Lauren Grychowski, Erkin Ozel, Anika Thite, Jasper E Visser, Ellen J Hess, Sharon M Kolk, H A Jinnah","doi":"10.1093/stcltm/szaf032","DOIUrl":"10.1093/stcltm/szaf032","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSCs) are widely used to model human genetic diseases. The most common strategy involves collecting cells from relevant individuals and then reprogramming them into iPSCs. This strategy is very powerful, but finding enough individuals with a specific genetic disease can be challenging, especially since most are rare. In addition, making numerous iPSC lines is time-consuming and expensive. As a result, most studies have included relatively small numbers of iPSC lines, sometimes from the same individual. Considering the experimental variability obtained using different iPSC lines, there has been great interest in delineating the most efficient number of lines needed to achieve a robust and reproducible result. Several recommendations have been published, although most conclusions have been based on methods where experimental variance from individual cases is difficult to separate from technical issues related to the preparation of iPSCs. The current study used gene expression profiles determined by RNA sequencing (RNAseq) to empirically evaluate the impact of the number of unique individuals and the number of replicate iPSC lines from each individual for modeling Lesch-Nyhan disease (LND). This disease is caused by mutations in the HPRT1 gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyltransferase. Results for detecting disease-relevant changes in gene expression depended on the analytical method employed, and whether or not statistical procedures were used to address multiple iPSC lines from the same individual. In keeping with prior studies, the best results were obtained with iPSC lines from 3-4 unique individuals per group. In contrast to prior studies, results were improved with 2 lines per individual, without statistical corrections for duplicate lines from the same individual. In the current study where all lines were produced in parallel using the same methods, most variance in gene expression came from technical factors unrelated to the individual from whom the iPSC lines were prepared.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769097","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}