Regenerative Therapy最新文献

{"title":"Current application of tissue-engineered dermal scaffolds mimicking the extracellular matrix microenvironment in wound healing","authors":"Xinran Ding ,&nbsp;Sujie Xie ,&nbsp;Wei Zhang ,&nbsp;Yushu Zhu,&nbsp;Dayuan Xu,&nbsp;Shuyuan Xian,&nbsp;Hanlin Sun,&nbsp;Xinya Guo,&nbsp;Yixu Li,&nbsp;Jianyu Lu,&nbsp;Xirui Tong,&nbsp;Runzhi Huang,&nbsp;Shizhao Ji,&nbsp;Zhaofan Xia","doi":"10.1016/j.reth.2024.12.018","DOIUrl":"10.1016/j.reth.2024.12.018","url":null,"abstract":"<div><div>With the continuous advancement of materials science, cell biology, and biotechnology, tissue engineering has introduced novel solutions to traditional wound healing approaches, particularly demonstrating significant potential in addressing complex or non-healing wounds. One of the key technologies in this field, dermal scaffolds, serve as wound coverage materials that mimic the structural framework of the dermis. They primarily assume the function of extracellular matrix, providing space for cell attachment, migration, and proliferation, thus supporting cellular growth and regulating multiple biological processes in healing. Tissue engineering utilizes combinations of natural or synthetic scaffolds, seeded cells, or growth factors to induce distinct effects in angiogenesis, extracellular matrix deposition, and functional recovery. Therefore, various bioengineered dermal scaffolds hold significant potential for clinical translation in wound healing. This review outlines various extracellular matrix molecules utilized in the development of dermal scaffolds, emphasizes recent progress in cell- and growth factor-modified scaffolds, and discusses the challenges and future perspectives in this evolving field.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 371-382"},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin prevents the loss of chondrogenic capacity in expansion cultured human auricular chondrocytes by alleviating mitochondrial dysfunction","authors":"Hua Tong ,&nbsp;Xudong Guo ,&nbsp;Lili Chen ,&nbsp;Honglei Wang ,&nbsp;Xuerui Hu ,&nbsp;Aijuan He ,&nbsp;Chenlong Li ,&nbsp;Tianyu Zhang ,&nbsp;Jiuhong Kang ,&nbsp;Yaoyao Fu","doi":"10.1016/j.reth.2025.01.005","DOIUrl":"10.1016/j.reth.2025.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the characteristics of cellular senescence in human auricular chondrocytes during long-term in vitro culture and to evaluate the effects of anti-senescence treatments on enhancing their chondrogenic function.</div></div><div><h3>Methods</h3><div>Auricular chondrocytes exhibited senescence-related characteristics after prolonged expansion in culture. To identify senescence inducers, transcriptome sequencing was performed, with findings corroborated by transmission electron microscopy analyses. Quercetin was employed as an intervention to mitigate cellular senescence progression. The alterations in cellular senescence and mitochondrial function were evaluated. Regenerative cartilage tissue was developed through in vitro chondrogenic induction and in vivo implantation with GelMA hydrogel-loaded cells in nude mice. The impact of quercetin was substantiated through histological examinations.</div></div><div><h3>Results</h3><div>Mitochondrial dysfunction was a key characteristic of auricular chondrocytes after long-term expansion culture. Chondrocytes cultured with quercetin showed a lower proportion of senescent cells and reduced mitochondrial dysfunction. The chondrocytes cultured with continuous application of quercetin formed higher quality regenerative cartilage both in vitro and in vivo compared to the control group.</div></div><div><h3>Conclusion</h3><div>The results reveal that quercetin attenuates chondrocyte senescence by alleviating mitochondrial dysfunction, thereby preventing the loss of chondrogenic function in chondrocytes subjected to long-term expansion culture.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 358-370"},"PeriodicalIF":3.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable preparation of in vivo transplantable periodontal ligament-derived mesenchymal stem cell sheets in thermoresponsive culture dishes with tunable cell detachability","authors":"Kazuki Morita ,&nbsp;Masamichi Nakayama ,&nbsp;Jiacheng Wang ,&nbsp;Satoru Onizuka ,&nbsp;Masahiro Hatasa ,&nbsp;Yujin Ohsugi ,&nbsp;Yosuke Tsuchiya ,&nbsp;Hiromi Niimi ,&nbsp;Anhao Liu ,&nbsp;Hideaki Sakai ,&nbsp;Teruo Okano ,&nbsp;Takanori Iwata","doi":"10.1016/j.reth.2025.01.004","DOIUrl":"10.1016/j.reth.2025.01.004","url":null,"abstract":"<div><div>Tissue engineering plays a pivotal role in the advancement of regenerative medicine. Thermoresponsive culture dishes, coated with specialized polymers that control cell adhesion through temperature fluctuations, enable the processing of cells into sheets for medical applications while maintaining their intact state. Cell sheets prepared using these culture dishes have been incorporated into several commercial pharmaceutical products. However, controlling the detachability of cell sheets using conventional thermoresponsive culture dishes remains a challenge, and often leads to unexpected detachment during cultivation. In this study, we developed a thermoresponsive culture dish with tunable cell detachability using a thermoresponsive block copolymer, poly(butyl methacrylate)-<em>b</em>-poly(<em>N</em>-isopropylacrylamide) (PBMA-PIPAAm), which is a specialized polymer that allows precise control of the amount of surface-immobilized polymer and polymer layer thickness. Culturing periodontal ligament-derived mesenchymal stem cells on these dishes demonstrated fully tunable detachability without compromising cell properties compared to conventional thermoresponsive dishes (UpCell®). Thermoresponsive PBMA-PIPAAm-coated culture dishes enable the complete on-demand detachment of transplantable cell sheets, thereby avoiding unexpected detachment that may increase production costs and reduce technical hurdles in the manufacturing process. The PBMA-PIPAAm coating method has the potential to contribute to biomedical and clinical applications of mesenchymal stem cell sheets.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 345-357"},"PeriodicalIF":3.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The next generation of regenerative dentistry: From tooth development biology to periodontal tissue, dental pulp, and whole tooth reconstruction in the clinical setting","authors":"Kazuki Morita ,&nbsp;Jiacheng Wang ,&nbsp;Keisuke Okamoto ,&nbsp;Takanori Iwata","doi":"10.1016/j.reth.2025.01.002","DOIUrl":"10.1016/j.reth.2025.01.002","url":null,"abstract":"<div><div>In modern dentistry, prosthetic approaches such as implants and dentures have been developed as symptomatic solutions for tooth loss. However, the complete regeneration of teeth and periodontal tissue, an ultimate aspiration of humanity, remains unachieved. Recent advancements in fundamental scientific technologies, including single-cell RNA sequencing and spatial transcriptomics, have significantly advanced our molecular understanding of tooth development, paving the way toward achieving this goal. This review summarizes the fundamental processes of tooth development in humans and mice, recent findings from basic research, and current clinical applications in dental regenerative medicine, including periodontal, alveolar bone, and dental pulp regeneration using cellular approaches.</div><div>Building on accumulated scientific knowledge, the complete regeneration of teeth and periodontal tissues may be achievable in the near future. We discuss the potential of emerging approaches, such as organoids derived from pluripotent stem cells and xenotransplantation using genetically modified animals, to transform dental medicine. These innovative concepts and integrated technologies hold the promise of enabling the regeneration of fully functional teeth and periodontal tissues.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 333-344"},"PeriodicalIF":3.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond conventional therapies: MSCs in the battle against nerve injury","authors":"Shuo Song ,&nbsp;Cong Li ,&nbsp;Ya Xiao ,&nbsp;Ziyu Ye ,&nbsp;Mingdeng Rong ,&nbsp;Jincheng Zeng","doi":"10.1016/j.reth.2024.12.017","DOIUrl":"10.1016/j.reth.2024.12.017","url":null,"abstract":"<div><div>Nerve damage can cause abnormal motor and sensory consequences, including lifelong paralysis if not surgically restored. The yearly cost of healthcare in the United States is projected to be $150 billion, and millions of Americans suffer from peripheral nerve injuries as a result of severe traumas and disorders. For nerve injuries, the outcome of conventional therapies is suboptimal and may have unfavorable side effects. However, mesenchymal stem cells (MSCs) have been proven to be a viable option for the reconstruction of injured nerve tissue and bring a ray of hope. These stem cells are derived from bone marrow, adipose tissue, and human umbilical cord blood and have the ability to secrete trophic factors, contribute to the immune system, and stimulate axonal regeneration. The purpose of this review is to examine the potential benefits of MSCs for enhancing functional recovery and patient prognosis by highlighting their characteristics and elucidating their mechanism of action in nerve injury healing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 280-291"},"PeriodicalIF":3.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing robustness of in vitro assay for immnosuppressive effect of mesenchymal stromal/stem cells: The role of inflammatory cytokine production by peripheral blood mononuclear cells","authors":"Rumi Sawada ,&nbsp;Shinji Kusakawa ,&nbsp;Mika Kusuhara ,&nbsp;Kazusa Tanaka ,&nbsp;Takumi Miura ,&nbsp;Satoshi Yasuda ,&nbsp;Yoji Sato","doi":"10.1016/j.reth.2024.12.016","DOIUrl":"10.1016/j.reth.2024.12.016","url":null,"abstract":"<div><h3>Introduction</h3><div>The Quality by Design (QbD) approach for developing cell therapy products using mesenchymal stromal/stem cells (MSCs) is a promising method for designing manufacturing processes to improve the quality of MSC products. It is crucial to ensure the reproducibility and robustness of the test system for evaluating critical quality attributes (CQAs) in the QbD approach for manufacturing of pharmaceutical products. In this study, we explored the key factors involved in establishing a robust evaluation system for the immunosuppressive effect of MSCs, which can be an example of a CQA in developing and manufacturing therapeutic MSCs for treating graft-versus-host disease, <em>etc</em>, and we have identified method attributes to increase the robustness of a simple <em>in vitro</em> assay to assess the immunosuppressive effects of MSCs.</div></div><div><h3>Methods</h3><div>We evaluated the performance of an assay system to examine the proliferation of peripheral blood mononuclear cells (PBMCs) activated with the mitogen phytohemagglutinin (PHA) when co-cultured with MSCs, the so-called one-way mixed lymphocyte reaction (MLR) assay. The MLR assay was performed on the same MSCs using 10 PBMC lots from different donors. In addition, 13 cytokine production levels in PHA-stimulated PBMCs were assessed.</div></div><div><h3>Results</h3><div>The PHA-stimulated proliferation response of PBMCs, the action of MSCs in the MLR test, and the cytokine release of the respective PBMCs significantly differed among the PBMC lots (p &lt; 0.05). A correlation analysis between the amounts of cytokines released by PBMCs and the immunosuppressive potency of MSCs showed that IFNγ, TNFα, CXCL10, PD-L1, HGF, and CCL5 production in PBMCs was significantly correlated with the MSC-mediated inhibition of PBMC proliferation (p &lt; 0.05). Therefore, we selected two PBMC lots with high PBMC proliferation and PHA-stimulated cytokine (such as IFNγ and TNFα) release for the subsequent one-way MLR assay. The robustness of the established test system was confirmed by repeating the assay several times on different days for the same MSCs (coefficient of variation &lt;0.2).</div></div><div><h3>Conclusions</h3><div>To make robust the MSC immunosuppressive potency assay system, controlling the quality of PBMCs used for the assay is essential. Evaluating the inflammatory cytokine production capacity of PBMCs is effective in assessing the quality of the MLR assay system.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 321-332"},"PeriodicalIF":3.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative gastrointestinal organoid models across species: A Zoobiquity approach for precision medicine","authors":"Masaya Tsukamoto ,&nbsp;Hidenori Akutsu","doi":"10.1016/j.reth.2024.12.013","DOIUrl":"10.1016/j.reth.2024.12.013","url":null,"abstract":"<div><div>Gastrointestinal (GI) health underpins systemic well-being, yet the complexity of gut physiology poses significant challenges to understanding disease mechanisms and developing effective, personalized therapies. Traditional models often fail to capture the intricate interplay between epithelial, mesenchymal, immune, and neuronal cells that govern gut homeostasis and disease. Over the past five years, advances in organoid technology have created physiologically relevant, three-dimensional GI models that replicate native tissue architecture and function. These models have revolutionized the study of autoimmune disorders, homeostatic dysfunction, and pathogen infections, such as norovirus and <em>Salmonella</em>, which affect millions of humans and animals globally. In this review, we explore how organoids, derived from intestinal and pluripotent stem cells, are transforming our understanding of GI development, disease etiology, and therapeutic innovation. Through the “Zoobiquity” paradigm and “One Health” framework, we highlight the integration of companion animal organoids, which provide invaluable insights into shared disease mechanisms and preclinical therapeutic development. Despite their promise, challenges remain in achieving organoid maturation, expanding immune and neuronal integration, and bridging the gap between organoid responses and <em>in vivo</em> outcomes. By refining these cutting-edge platforms, we can advance human and veterinary medicine alike, fostering a holistic approach to health and disease.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 314-320"},"PeriodicalIF":3.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of chimeric antigen receptor T cells targeting cancer-expressing podocalyxin","authors":"Yuta Mishima ,&nbsp;Shintaro Okada ,&nbsp;Akihiro Ishikawa ,&nbsp;Bo Wang ,&nbsp;Masazumi Waseda ,&nbsp;Mika K. Kaneko ,&nbsp;Yukinari Kato ,&nbsp;Shin Kaneko","doi":"10.1016/j.reth.2024.12.010","DOIUrl":"10.1016/j.reth.2024.12.010","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized the treatment of CD19-positive B-cell malignancies. However, the field is rapidly evolving to target other antigens, such as podocalyxin (PODXL), a transmembrane protein implicated in tumor progression and poor prognosis in various cancers. This study explores the potential of PODXL-targeted CAR-T cells, utilizing a cancer-specific monoclonal antibody (CasMab) technique to enhance the specificity and safety of CAR-T cell therapy. We developed CAR-T cells based on the single-chain variable fragment (scFv) derived from the cancer-specific monoclonal antibody PcMab-6, which selectively targets glycosylation modifications on PODXL-expressing cancer cells. As a control, CAR-T cells were also generated from PcMab-47, a non-cancer-specific antibody for PODXL. <em>In vitro</em> experiments demonstrated that CAR-T cells based on PcMab-6 exhibited significant antitumor activity with reduced off-target effects on normal cells compared to PcMab-47-derived CAR-T cells. Additionally, to enhance the persistence and therapeutic efficacy of these CAR-T cells, we developed a humanized version of PcMab-6 scFv. The humanized CAR-T cells showed extended antitumor effects <em>in vivo</em>, demonstrating the potential for prolonged therapeutic activity. These findings underscore the utility of CasMab technology in generating highly specific and safer CAR-T cell therapies for solid tumors, highlighting the promise of humanized CAR-T cells for clinical application.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 292-300"},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canine adipose-derived mesenchymal stromal cells inhibit the growth of canine hematologic malignancy cell lines","authors":"Yuyo Yasumura ,&nbsp;Takahiro Teshima ,&nbsp;Tomokazu Nagashima ,&nbsp;Masaki Michishita ,&nbsp;Hiroki Shigechika ,&nbsp;Yoshiaki Taira ,&nbsp;Ryohei Suzuki ,&nbsp;Hirotaka Matsumoto","doi":"10.1016/j.reth.2024.12.019","DOIUrl":"10.1016/j.reth.2024.12.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Intestinal lymphoma may be latent in some dogs with chronic inflammatory enteropathy. Mesenchymal stromal cells (MSCs) have potential therapeutic applications for refractory chronic inflammatory enteropathy, but their impact on the development of potential intestinal lymphomas has not yet been evaluated. Therefore, this study was performed to investigate the effect of canine adipose-derived MSCs (cADSCs) on the growth of canine lymphoma cell lines to assess the safety of MSC-based therapy in terms of pro- and anti-tumorigenic effects.</div></div><div><h3>Methods</h3><div>CADSCs were co-cultured with canine lymphoma/leukemia cell lines of various lineages, with or without cell-to-cell contact, to evaluate their effects on proliferation, apoptosis, and cell cycle progression in vitro. Additionally, a bioluminescent canine lymphoma cell line, established through firefly luciferase transduction, was co-injected with varying doses of cADSCs into immunocompromised mice. The growth of canine lymphoma cells was monitored over time in vivo using bioluminescence imaging.</div></div><div><h3>Results</h3><div>CADSCs inhibited the proliferation of all canine lymphoma/leukemia cell lines in a dose-dependent manner in vitro, under conditions allowing cell-to-cell contact. This inhibition occurred via the induction of apoptosis, G0/G1 phase cell cycle arrest, or both mechanisms. However, these effects were lost when the cells were physically separated using Transwell inserts. In xenotransplantation mouse models, cADSCs dose-dependently inhibited canine lymphoma cell growth and lung metastasis, as indicated by reduced bioluminescence signals.</div></div><div><h3>Conclusions</h3><div>This study has demonstrated for the first time that cADSCs inhibit the growth of different lineages of canine lymphoma/leukemia cells both in vitro and in vivo. These findings suggest that MSC-based cell therapy could potentially be applied to canine chronic inflammatory enteropathy without increasing the risk of promoting the growth of latent intestinal lymphomas.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 301-313"},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells improves cardiac function through extracellular vesicle-mediated tissue repair in a rat model of ischemic cardiomyopathy","authors":"Ryo Kawasumi ,&nbsp;Takuji Kawamura ,&nbsp;Kizuku Yamashita ,&nbsp;Yuji Tominaga ,&nbsp;Akima Harada ,&nbsp;Emiko Ito ,&nbsp;Maki Takeda ,&nbsp;Shunbun Kita ,&nbsp;Iichiro Shimomura ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2024.12.008","DOIUrl":"10.1016/j.reth.2024.12.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) has a therapeutic effect on myocardial ischemia. However, the therapeutic mechanism underlying systemic iPS-MSC-based therapy for ischemic cardiomyopathy (ICM) remains unclear. We investigated the therapeutic effects of iPS-MSCs through extracellular vesicle (EV)-mediated tissue repair in a rat model of ICM.</div></div><div><h3>Methods</h3><div>A rat ICM model was created by left anterior descending coronary artery ligation. iPS-MSCs were administered intravenously every week for four weeks in the iPS-MSC group, whereas saline was administered to the control group. Alix, a protein involved in the biogenesis of EVs, was knocked down, and Alix-knockdown iPS-MSCs were administered to the siAlix group. We analyzed sequential cardiac function using echocardiography, histological analysis, cell tracking analysis with fluorescent dyes, and comprehensive RNA sequencing of the border zone of the myocardium after treatment.</div></div><div><h3>Results</h3><div>Left ventricular ejection fraction (LVEF) was significantly improved in the iPS-MSC group compared with that in the control group. In the siAlix group, LVEF was significantly lower than that in the iPS-MSC group. Histological analysis showed a significant decrease in fibrosis area and significant increase in microvascular density in the iPS-MSC group. A cell-tracking assay revealed iPS-MSC accumulation in the border zone of the myocardium during the acute phase. Comprehensive microRNA sequencing analysis revealed that EVs from iPS-MSCs contained miRNAs associated with anti-fibrosis and angiogenesis. Gene ontology analysis of differentially expressed genes in myocardial tissue also showed upregulation of pathways related to antifibrosis and neovascularization and downregulation of pathways linked to inflammation and T-cell differentiation.</div></div><div><h3>Conclusions</h3><div>Systemic administration of iPS-MSCs improved cardiac function through EV-mediated angiogenetic and antifibrotic effects in an ICM, suggesting the clinical possibility of treating chronic heart failure.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 253-261"},"PeriodicalIF":3.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}