Stem Cell Research & Therapy最新文献

{"title":"A chitosan/acellular matrix-based neural graft carrying mesenchymal stem cells to promote peripheral nerve repair.","authors":"Zhifa Zhang, Molin Li, Gang Cheng, Peng Wang, Chunhui Zhou, Yang Liu, Xiaofeng Duan, Jing Wang, Fang Xie, Yaqiong Zhu, Jianning Zhang","doi":"10.1186/s13287-024-04093-5","DOIUrl":"10.1186/s13287-024-04093-5","url":null,"abstract":"<p><strong>Background: </strong>Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects.</p><p><strong>Methods: </strong>Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats.</p><p><strong>Results: </strong>In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery.</p><p><strong>Conclusions: </strong>Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"503"},"PeriodicalIF":7.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907659","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":"Research advances in the construction of stem cell-derived ovarian organoids.","authors":"Tianyue Zhang, Mengtong Zhang, Sichen Zhang, Shaowei Wang","doi":"10.1186/s13287-024-04122-3","DOIUrl":"10.1186/s13287-024-04122-3","url":null,"abstract":"<p><p>Ovarian organoids are essential in female reproductive medicine, enhancing our understanding of ovarian diseases and improving treatments, which benefits women's health. Constructing ovarian organoids involves two main processes: differentiating induced pluripotent stem cells (iPSCs) into germ and ovarian somatic cells to restore ovarian function and using extracellular matrix (ECM) to create a suitable ovarian microenvironment and scaffold. Although the technology is still in its early stages, future advancements will likely involve integrating high-throughput analysis, 3D-printed scaffolds, and efficient iPSC induction, driving progress in reproductive and regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"505"},"PeriodicalIF":7.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907665","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":"Enhanced fetal hemoglobin production via dual-beneficial mutation editing of the HBG promoter in hematopoietic stem and progenitor cells for β-hemoglobinopathies.","authors":"Prathibha Babu Chandraprabha, Manoj Kumar K Azhagiri, Vigneshwaran Venkatesan, Wendy Magis, Kirti Prasad, Sevanthy Suresh, Aswin Anand Pai, Srujan Marepally, Alok Srivastava, Kumarasamypet Murugesan Mohankumar, David I K Martin, Saravanabhavan Thangavel","doi":"10.1186/s13287-024-04117-0","DOIUrl":"10.1186/s13287-024-04117-0","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased. However, achieving this goal requires precise nucleotide conversions in hematopoietic stem and progenitor cells (HSPCs) at therapeutic efficiency, which remains a challenge.</p><p><strong>Methods: </strong>We employed Cas9 RNP-ssODN-mediated homology-directed repair (HDR) gene editing to mimic two naturally occurring HBG promoter point mutations; -175T > C, associated with high HbF levels, and -158 C > T, a common polymorphism in the Indian population that induces HbF under erythropoietic stress, in HSPCs.</p><p><strong>Results: </strong>Asymmetric, nontarget ssODN induced high rates of complete HDR conversions, with at least 15% of HSPCs exhibiting both the -175T > C and -158 C > T mutations. Optimized conditions and treatment with the small molecule AZD-7648 increased this rate, with up to 57% of long-term engrafting human HSPCs in NBSGW mice containing at least one beneficial mutation. Functionally, in vivo erythroblasts exhibited high levels of HbF, which was sufficient to reverse the cellular phenotype of β-thalassemia. Further support through bone marrow MSC co-culture boosted complete HDR conversion rates to exceed 80%, with minimal InDels, improved cell viability, and induced fetal hemoglobin levels similar to those of Cas9 RNP-mediated indels at BCL11A enhancer and HBG promoter.</p><p><strong>Conclusions: </strong>Cas9 RNP-ssODN-based nucleotide conversion at the HBG promoter offers a promising gene therapy approach to ameliorate the phenotypes of β-thalassemia and SCD. The developed approach can simplify and broaden applications that require the cointroduction of multiple nucleotide modifications in HSPCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"504"},"PeriodicalIF":7.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907664","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 umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.","authors":"Yafei Lu, Shaohua Huangfu, Chuanxue Ma, Yan Ding, Yajie Zhang, Chungen Zhou, Lianming Liao, Ming Li, Jia You, Yuting Chen, Dawei Wang, Ao Chen, Bin Jiang","doi":"10.1186/s13287-024-04028-0","DOIUrl":"10.1186/s13287-024-04028-0","url":null,"abstract":"<p><strong>Background: </strong>Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.</p><p><strong>Methods: </strong>This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.</p><p><strong>Results: </strong>The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.</p><p><strong>Conclusions: </strong>The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"414"},"PeriodicalIF":7.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898276","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":"Generation of vascularized pancreatic progenitors through co-differentiation of endoderm and mesoderm from human pluripotent stem cells.","authors":"Xiaopu Sang, Junming Xu, Yihang Wang, Jingyi Li, Jiasen Xu, Xiaoni Chen, Xianjie Shi, Fenfang Wu","doi":"10.1186/s13287-024-04120-5","DOIUrl":"10.1186/s13287-024-04120-5","url":null,"abstract":"<p><strong>Background: </strong>The simultaneous differentiation of human pluripotent stem cells (hPSCs) into both endodermal and mesodermal lineages is crucial for developing complex, vascularized tissues, yet poses significant challenges. This study explores a method for co-differentiation of mesoderm and endoderm, and their subsequent differentiation into pancreatic progenitors (PP) with endothelial cells (EC).</p><p><strong>Methods: </strong>Two hPSC lines were utilized. By manipulating WNT signaling, we optimized co-differentiation protocols of mesoderm and endoderm through adjusting the concentrations of CHIR99021 and mTeSR1. Subsequently, mesoderm and endoderm were differentiated into vascularized pancreatic progenitors (vPP) by adding VEGFA. The differentiation characteristics and potential of vPPs were analyzed via transcriptome sequencing and functional assays.</p><p><strong>Results: </strong>A low-dose CHIR99021 in combination with mTeSR1 yielded approximately 30% mesodermal and 70% endodermal cells. Introduction of VEGFA significantly enhanced EC differentiation without compromising PP formation, increasing the EC proportion to 13.9%. Transcriptomic analyses confirmed the effectiveness of our protocol, showing up-regulation of mesodermal and endothelial markers, alongside enhanced metabolic pathways. Functional assays demonstrated that vPPs could efficiently differentiate into insulin-producing β-cells, as evidenced by increased expression of β-cell markers and insulin secretion.</p><p><strong>Conclusion: </strong>Our findings provide a robust method for generating vPPs, which holds significant promise for regenerative medicine applications, particularly in diabetes treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"502"},"PeriodicalIF":7.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885947","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":"Correction: POU3F4 up-regulates Gli1 expression and promotes neuronal differentiation and synaptic development of hippocampal neural stem cells.","authors":"Lei Zhang, Jue Wang, Naijuan Xu, Jingjing Guo, Yujian Lin, Xunrui Zhang, Ruijie Ji, Yaya Ji, Haoming Li, Xiao Han, Wen Li, Xiang Cheng, Jianbing Qin, Meiling Tian, Min Xu, Xinhua Zhang","doi":"10.1186/s13287-024-04112-5","DOIUrl":"10.1186/s13287-024-04112-5","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"501"},"PeriodicalIF":7.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885914","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":"Correction: Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species.","authors":"Juntao Fang, Qiangbing Yang, Renée G C Maas, Michele Buono, Bram Meijlink, Dyonne Lotgerink Bruinenberg, Ernest Diez Benavente, Michal Mokry, Alain van Mil, Li Qian, Marie-José Goumans, Raymond Schiffelers, Zhiyong Lei, Joost P G Sluijter","doi":"10.1186/s13287-024-04113-4","DOIUrl":"10.1186/s13287-024-04113-4","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"500"},"PeriodicalIF":7.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885916","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":"Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions.","authors":"Kai Chen, Yanyan Gao, Ninuo Xia, Yusheng Liu, Huiru Wang, Hui Ma, Shengxia Zheng, Fang Fang","doi":"10.1186/s13287-024-04100-9","DOIUrl":"10.1186/s13287-024-04100-9","url":null,"abstract":"<p><strong>Background: </strong>Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for most of the pre-clinical experiments performed on multiple animal models, as human-derived eMSC cannot maintain long-term engraftment in animals. Whether tissue-specific MSCs from allogeneic origin can engraft and exert long-term therapeutic efficacy has yet to be thoroughly explored.</p><p><strong>Methods: </strong>We established a rat IUA model to study the long-term engraftment and therapeutic effects of eMSC derived from humans and rats. Human and rat eMSC were isolated and verified by the expression of cell surface markers and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. The cells were then labeled by green fluorescence proteins (GFP) and transplanted to the rat uterus ex vivo and in vivo. The engraftment was investigated by the expression of GFP at different days after transplantation. Assessed the therapeutic effects by examining the endometrial thickness, the number of glands, and the pregnancy outcome. Significantly, we conducted a thorough assessment of the local cellular immune response following both xenograft and allograft transplantation.</p><p><strong>Results: </strong>H-eMSC were eliminated by rats' immune systems within three days after transplantation. In constrast, R-eMSC successfully engrafted and persisted in rat tissue for over ten days. Notably, R-eMSC significantly improved the pregnancy rate by enhancing endometrial thickness and increasing the number of glands, while also reducing fibrosis in rat IUA models. Additionally, the immune response to R-eMSC was generally less aggressive compared to that of xenogeneic MSCs.</p><p><strong>Conclusions: </strong>Tissue-specific MSCs from the allogeneic origin can integrate into the repaired tissue and exert long-term therapeutic efficacy in the model of IUA. This study indicates that in addition to secreting therapeutic factors short-time, tissue-specific MSCs may engraft and participate in long-time tissue repair and regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"499"},"PeriodicalIF":7.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882987","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":"Therapeutic potential of placenta-derived stem cells cultivated on noggin-loaded nanochitosan/polypyrrole-alginate conductive scaffold to restore spinal cord injury.","authors":"Asma Manzari-Tavakoli, Amirhesam Babajani, Nasim Vousooghi, Ali Moghimi, Roghayeh Tarasi, Fahimeh Safaeinejad, Samira Norouzi, Soheyl Bahrami, Hassan Niknejad","doi":"10.1186/s13287-024-04104-5","DOIUrl":"10.1186/s13287-024-04104-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Spinal cord injury (SCI) is a severe and permanent nerve damage condition that poses significant burdens on individuals and society. Various therapeutic approaches have been explored to mitigate the consequences of SCI. Tissue engineering and regenerative medicine have emerged as a promising avenue for addressing this issue. This study aims to investigate the potential of a nanochitosan/polypyrrole-alginate conductive scaffold, loaded with the Noggin growth factor, an inhibitor of BMP-4 signaling, and human amniotic epithelial cells (hAECs), in promoting the regeneration of SCI in animal models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The attachment and distribution of isolated hAECs on a fabricated nanochitosan/polypyrrole-alginate conductive scaffold were assessed using SEM. Additionally, the neural differentiation of hAECs on the scaffold was investigated by analyzing the expression of specific neuronal (Calca, Fox3), oligodendrocyte (MBP), and astrocyte (GFAP) genes in vitro. To evaluate the combined effect of the scaffold and Noggin growth factor in animal models, a Noggin-loaded scaffold was designed using bioinformatics, and the loading and release capacity of Noggin were measured. For in vivo studies, rats underwent laminectomy and were transplanted with the scaffold, either alone or with Noggin and DII labeled- hAECs, at the T10-T11 level. Motor functions of the animal were evaluated using BBB scoring weekly in an open field for four weeks. Furthermore, the expression of neural genes and immunohistochemical tests were evaluated after four weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;hAECs exhibited uniform distribution and attachment to the scaffold. In vitro differentiation analyses showed increased expression of Calca, Fox3, MBP, and GFAP genes. Docking results indicated that Noggin could interact with chitosan nanoparticles through hydrogen bonds. The chitosan nanoparticles effectively loaded 22.6% of exposed Noggin, and the scaffold released 28.5% of the total incorporated Noggin. In vivo studies demonstrated that transplanting nanochitosan/polypyrrole-alginate conductive scaffolds with DII labeled-hAECs, with or without Noggin, improved motor functions in animal models. The assessment of gene expression patterns in transplanted hAECs revealed that neuronal (Calca, Fox3) and oligodendrocyte (MBP) genes in the injured spinal cord of the animal models were upregulated. Histopathological analysis showed a reduction in inflammation and glial scar formation, while neural fiber regeneration increased in the treated animals. Also, DII labeled-hAECs in the lesion site were alive after a period of four weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Based on these findings, it can be inferred that the integrative therapeutic effects of human amniotic epithelial cells, nanochitosan/polypyrrole-Alginate conductive scaffold, and Noggin (as BMP-4 signaling inhibitor) represents a promising and innovative approach in the field of transl","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"497"},"PeriodicalIF":7.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882989","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 study of novel human allogeneic adipose tissue-derived mesenchymal stem cell sheets toward a first-in-human clinical trial for myopic chorioretinal atrophy.","authors":"Norimichi Nagano, Yoshio Hirano, Masayo Kimura, Hiroshi Morita, Tsutomu Yasukawa","doi":"10.1186/s13287-024-04118-z","DOIUrl":"10.1186/s13287-024-04118-z","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells may have neuroprotective and tissue regenerative capabilities and the potential to rescue retinal degeneration in chorioretinal diseases including myopic chorioretinal atrophy. Transplantation of human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) suspensions has been clinically conducted to treat retinal degenerative diseases. However, serious side effects including proliferative vitreoretinopathy and epiretinal membrane formation have been reported. PharmaBio Corporation fabricated novel adMSC sheets with a Bruch's membrane-like structure using our original method, potentially overcoming these problems. We evaluated the characteristics of newly developed adMSC sheets named PAL-222 and assessed their safety and efficacy in rats with congenital retinal degeneration (RCS rats) to obtain the proof-of-concept for the first-in-human clinical trial for myopic chorioretinal atrophy.</p><p><strong>Methods: </strong>We measured the viability of cells obtained from PAL-222, examined cell surface antigens by flow cytometry, measured the vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) secretory ability, examined the expression of types I and IV collagen and elastin by immunostaining. We performed a transwell in vitro migration assay to evaluate durability and similarity to retinal pigment epithelium (RPE) and checked in vitro tumorigenicity. In an in vivo experiment, we transplanted PAL-222 into the subretinal space of RCS rats and evaluated the safety and efficacy.</p><p><strong>Results: </strong>Viability of cells obtained from PAL-222 was 88.1%. The rate of positive markers such as CD90, CD73, CD105 and CD44 exceeded 90%; that of the negative markers such as CD34, CD11b, CD19, CD45 and HLA-DR was less than 2%. PAL-222 secreted significant amounts of VEGF and PEDF and expressed types I and IV collagen and elastin. The migration assay showed that PAL-222 preserved the sheet structure without cell migration. No chromosomal aberration or colony formation was observed in in vitro tumorigenicity tests. PAL-222 transplantation suppressed the progression of retinal degeneration by preserving the outer nuclear layer without negative changes in RCS rats, suggesting a retinoprotective effect.</p><p><strong>Conclusions: </strong>We confirmed the efficacy and safety of PAL-222 and are currently conducting a clinical trial to treat myopic chorioretinal atrophy. Transplantation of these novel adMSC sheets may be a promising therapy for myopic chorioretinal atrophy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, Identifier: NCT05658237. URL: https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05658237 .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"498"},"PeriodicalIF":7.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882988","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}