Regenerative Therapy最新文献

{"title":"Global research dynamics in the induced pluripotent stem cell and diabetes: A bibliometric analysis of the past twenty years","authors":"Jiatong Wang,&nbsp;Sirui Huang,&nbsp;Kaiyuan Li,&nbsp;Jing Li,&nbsp;Xin Huang","doi":"10.1016/j.reth.2025.06.015","DOIUrl":"10.1016/j.reth.2025.06.015","url":null,"abstract":"<div><h3>Objectives</h3><div>Induced pluripotent stem cells (iPSCs) have the potential to differentiate into insulin-producing β cells, offering a promising avenue for the treatment and research of diabetes. However, a comprehensive quantitative analysis of their specific impact in the field of diabetes has yet to be conducted. This study aims to analyze the current status and research hotspots of induced pluripotent stem cells in the field of diabetes over the past two decades, providing a reference for future research directions.</div></div><div><h3>Methods</h3><div>This study performed a bibliometric analysis of recent literature on induced pluripotent stem cells in the field of diabetes, with data sourced from the Web of Science database. Using R software and VOSviewer, keyword clustering and research themes were analyzed to uncover trends and frontiers in this field.</div></div><div><h3>Results</h3><div>The research included a total of 610 studies on induced pluripotent stem cells in the field of diabetes. In recent years, research in this field has shown a global upward trend, with the number of publications experiencing exponential growth from 2008 to 2021. However, the period from 2022 to 2025 is expected to be a plateau phase with fluctuations, gradually slowing down. The United States is the leading country in terms of publications, followed by China, Japan, the United Kingdom, and Italy. The United States not only leads in the number of publications but also has a broader network of international collaborators. Stem Cell Research and Diabetes are the most frequently published and cited journals. Currently, the application of iPSCs in studying the pathological mechanisms of diabetes and disease modeling has become a research hotspot. iPSCs provide an important in vitro platform for understanding the pathogenesis of diabetes and can also be used for drug screening, gene expression profiling, and studying the degeneration process of β-cells. Additionally, the use of iPSCs in the generation and regeneration of pancreatic β-cells, as a frontier of regenerative medicine and stem cell therapy, demonstrates the potential to restore normal islet function in diabetic patients. Furthermore, integrating immune evasion mechanisms and gene therapy, particularly by enhancing islet cell survival and function through immune regulation and genetic modification, is emerging as a new direction for diabetes treatment.</div></div><div><h3>Conclusion</h3><div>The differentiation of induced pluripotent stem cells into β cells may offer a pathway to curing diabetes. This article systematically analyzes the current status and research hotspots of induced pluripotent stem cells in the diabetes field, providing valuable references for future clinical practice and research.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 341-350"},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The umbilical cord blood exosome MFG-E8 alleviates hypoxic-ischemic encephalopathy brain injury in neonatal rats by restoring autophagy flux and inhibiting ferroptosis through GSK3β/β-catenin signaling","authors":"Menghua Zhao ,&nbsp;Yizhong Wu ,&nbsp;Li Huang ,&nbsp;Juanmei Wang ,&nbsp;Aimin Zhang","doi":"10.1016/j.reth.2025.06.016","DOIUrl":"10.1016/j.reth.2025.06.016","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have revealed importance of human umbilical cord blood (HUCB)-derived exosomes (HUCB-Exo) in central nervous system diseases, but the role of HUCB-Exo in hypoxic-ischemic encephalopathy (HIE) remains unclear. This study aims to explore the mechanisms of HUCB-Exo in HIE.</div></div><div><h3>Methods</h3><div>HIE models were constructed in 7-day-old neonatal rats using classical Rice-Vannucci modeling, and SH-SY5Y cells were induced by oxygen-glucose deprivation/reperfusion (OGD/R) injury, followed by intervention with HUCB and HUBC-Exo, either non-transfected or transfected with si-NC/si-MFG-E8.</div></div><div><h3>Results</h3><div>HUBC-Exo decreased cerebral infarct size and cerebral water content in HIE neonatal rats and improved short-term and long-term neurological function. HUBC-Exo down-regulated Beclin1, ATG7, and LC3 II/I expression, while promoting p62 expression in HIE neonatal rats. After HUBC-Exo treatment, NCOA4 and ACSL4 expression in HIE neonatal rats decreased, while FTH1, SLC7A11, and GPX4 expression were increased. In addition, HUBC-Exo decreased Fe²⁺, MDA, and ROS levels in HIE neonatal rats. Similarly, these <em>in vivo</em> results were observed <em>in vitro</em>. HUBC-Exo inhibited autophagy and ferroptosis in OGD/R-induced SH-SY5Y cells, and MFG-E8 silencing interrupted HUBC-Exo action. Further results showed that HUBC-Exo-derived MFG-E8 promoted p-GSK3β/GSK3β and Active-β-catenin/β-catenin levels in OGD/R-induced SH-SY5Y cells. Importantly, the GSK3β agonist LiCl revoked the promotion of HUBC-Exo^si-MFG-E8 on autophagy and ferroptosis in OGD/R-induced SH-SY5Y cells. HUBC-Exo MFG-E8 inhibited autophagy and ferroptosis, thereby alleviating brain damage in HIE neonatal rats.</div></div><div><h3>Conclusion</h3><div>Our results suggested that HUBC-Exo-transmitted MFG-E8 inhibited autophagy and ferroptosis through GSK3β/β-catenin signaling, thereby alleviating brain injury in HIE neonatal rats, which provided a new idea for treating HIE.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 321-332"},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplantation of adipose-derived stem cell aggregates via hydrogel microspheres that incorporate growth factors increases muscle strength","authors":"Tomohiro Abe ,&nbsp;Emiko Tanaka Isomura ,&nbsp;Toshie Kuwahara ,&nbsp;Ryo Mitsui ,&nbsp;Makoto Matsukawa ,&nbsp;Kiyoko Nakagawa ,&nbsp;Susumu Tanaka ,&nbsp;Yasuhiko Tabata","doi":"10.1016/j.reth.2025.05.016","DOIUrl":"10.1016/j.reth.2025.05.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Stem cell transplantation is widely employed to treat various diseases, and adipose-derived mesenchymal stem cells (ASCs) are used for allogeneic xenotransplantation. However, muscle function post stem cell transplantation remains largely understudied. Therefore, we aimed to investigate the optimal conditions for the transplantation of ASC aggregates of gelatin hydrogel microparticles incorporating growth factors. We further aimed to establish a method for improving muscle function via ASC implantation combined with muscle loading through treadmill running.</div></div><div><h3>Methods</h3><div>Mouse ASCs suspended in various solutions were transplanted into the soleus muscles. The strength of each mouse was measured using a digital force gauge after a muscle load was applied using a treadmill.</div></div><div><h3>Results</h3><div>Platelet-rich growth factor-BB (PDGF-BB) effectively facilitated the expression of MYO-D in the ASCs. Moreover, the injection of cell aggregates rather than suspensions enhanced cell retention. Transplantation of ASC-aggregate gelatin hydrogel microparticles incorporating PDGF-BB in combination with muscle load using a treadmill enhanced mouse muscle function.</div></div><div><h3>Conclusions</h3><div>ASC aggregates with growth factor transplantation likely enhance cell retention. Moreover, they likely improve muscle function and load. Thus, our findings provide new avenues for cell regeneration therapy in muscle rehabilitation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 299-308"},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the use of autologous exosomes and platelet-derived growth factors in women with premature ovarian insufficiency and infertility: A prospective, randomized, observational, analytical study","authors":"Carmen Navarro ,&nbsp;Pedro Torrecillas Cabrera ,&nbsp;Alejandro Teppa Garrán","doi":"10.1016/j.reth.2025.06.007","DOIUrl":"10.1016/j.reth.2025.06.007","url":null,"abstract":"<div><div>Stromal fibrosis and ovarian aging depend not only on the age of the patients but also on environmental factors, lifestyle and physiological events such as ovulation itself, which leaves repeated scarring in the ovarian stroma, limiting normal tissue vascularization and the provision of biological signals necessary to maintain folliculogenesis and hormone synthesis. In a fibrosed ovarian stroma, there is a decrease in hyaluronic acid concentrations, loss of synthesis and migration proteins, a decrease in microRNAs, in addition to enzymatic alterations that affect mitochondrial kinases, increasing oxygen free radicals, which accelerate cell death.</div></div><div><h3>Objectives</h3><div>This study seeks to analyze the effectiveness of autologous exosomes in reversing aging and bioregenerating the ovary of patients with ovarian failure and infertility by improving interstitial fibrosis and providing the necessary elements to activate neofolliculogenesis.</div></div><div><h3>Methodology</h3><div>Prospective, randomized, comparative study in 30 women between 38 and 46 years old, with diminished ovarian reserve and who rejected the egg donation procedure. Three study groups composed of 10 patients each: the first with autologous exosomes, the second with PRP and the third with saline solution.</div></div><div><h3>Results</h3><div>After completing the study, it was found that women in the Autologous Exosome group showed better ovarian reserve parameters such as FSH, LH, Estradiol, Anti-Müllerian Hormone and antral follicle count, edema of more oocytes collected in Metaphase II, higher fertilization rate, frozen embryos and positive pregnancies.</div></div><div><h3>Conclusion</h3><div>Ovarian Biostimulation with Autologous Exosomes could be considered a safe and promising therapy to improve markers of low ovarian reserve.</div></div><div><h3>Trial registration</h3><div>Clinical <span><span>Trials.gov</span><svg><path></path></svg></span>. Registration Number: NCT06773572. URL: Study Details | Use of Autologous Exosomes vs Platelet Growth Factors to Regenerate the Ovary in Women With Infertility (Exosomas2024-1) | ClinicalTrials.gov.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 309-320"},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative potential of PRP-based scaffolds in chronic wound healing: Mechanisms, advances, and therapeutic insights","authors":"Farag M.A. Altalbawy ,&nbsp;Bilal Abdul Majeed Mukhlif ,&nbsp;Ahemad Hussen ,&nbsp;Jaafaru Sani Mohammed ,&nbsp;Renuka Jyothi S ,&nbsp;Arshdeep Singh ,&nbsp;Shakti Bedanta Mishra ,&nbsp;Ashish Singh Chauhan ,&nbsp;Mohammad Ebrahim Astaneh ,&nbsp;Narges Fereydouni","doi":"10.1016/j.reth.2025.06.008","DOIUrl":"10.1016/j.reth.2025.06.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers often remain trapped in the inflammatory phase due to oxidative stress, protease overactivity, and impaired cellular responses, particularly in diabetic conditions. These wounds require advanced therapeutic strategies beyond conventional care. Regenerative medicine—especially platelet-rich plasma (PRP)-based interventions—has emerged as a promising approach for enhancing wound repair.</div></div><div><h3>Methods</h3><div>This review examines recent developments in PRP-loaded scaffolds, focusing on their biological mechanisms, structural advantages, and clinical applications. It synthesizes findings from key studies that integrate PRP with natural and synthetic biomaterials, often combined with bioactive agents like adipose-derived stem cell exosomes.</div></div><div><h3>Results</h3><div>PRP-containing scaffolds promote wound healing through multiple pathways: enhancing cell proliferation, migration, angiogenesis, and extracellular matrix remodeling; reducing inflammation via M2 macrophage polarization; and facilitating collagen deposition. Their antibacterial properties and controlled release of growth factors such as VEGF and TGF-β1 further support tissue regeneration. Additionally, scaffold composition improves mechanical strength, elasticity, and growth factor bioavailability. Innovations such as GelMA/SFMA hydrogels and COL/PRP-ADSC-exos composites have shown superior outcomes in preclinical models.</div></div><div><h3>Conclusions</h3><div>PRP-based scaffolds offer a multifunctional platform for chronic wound treatment by combining biological activity with structural support. Despite existing challenges such as variability in PRP preparation and limited clinical data, ongoing research and emerging technologies hold strong potential to standardize and enhance these therapies for future clinical translation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 278-298"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trehalose enhances neuronal differentiation with VEGF secretion in human iPSC-derived neural stem/progenitor cells","authors":"Sean K. Roose ,&nbsp;Yoichi Mizukami ,&nbsp;Jun Muto ,&nbsp;Hideyuki Okano ,&nbsp;Masaya Nakamura ,&nbsp;Narihito Nagoshi","doi":"10.1016/j.reth.2025.06.012","DOIUrl":"10.1016/j.reth.2025.06.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell transplantation therapy has emerged as a promising approach in regenerative medicine for treating neurological diseases. Neural stem/progenitor cell (NS/PC) transplantation has demonstrated therapeutic efficacy; however, its potential remains limited by suboptimal differentiation and insufficient secretion of pro-healing growth factors. Trehalose, a glucose disaccharide, has been shown to exert neuroprotective effects by inducing autophagy and stabilizing cellular structures. Recent studies suggest that trehalose can modulate growth factor secretion through the CDKN1A/p21 pathway. However, its impact on human induced pluripotent stem cell-derived NS/PCs (hiPSC-NS/PCs) remains unclear. This study investigates the effect of trehalose on neuronal differentiation, cell viability, and growth factor expression in hiPSC-NS/PCs to explore its potential in enhancing transplantation therapy.</div></div><div><h3>Methods</h3><div>hiPSC-NS/PCs were cultured as neurospheres and treated with trehalose (10 mg/ml or 40 mg/ml) for 7 days. Cell viability was assessed using CellTiter Glo® assay. Gene expression analysis was conducted via qRT-PCR and RNA-seq, particularly focusing on <em>CDKN1A</em>, <em>VEGFA</em>, <em>FGF2</em>, and <em>BDNF</em>. Protein expression of SOX2 was analyzed via western blotting. Neurite outgrowth was evaluated using MAP2 immunostaining following differentiation. Statistical significance was set at p &lt; 0.05.</div></div><div><h3>Results</h3><div>Treatment with 10 mg/ml trehalose upregulated <em>CDKN1A</em> expression and promoted neuronal differentiation, as evidenced by reduced SOX2 expression and enhanced neurite outgrowth. RNA-seq analysis revealed the activation of growth factor-related pathways, including <em>VEGFA</em> upregulation, which persisted even after trehalose withdrawal (p = 0.016). However, high concentration (40 mg/ml) significantly reduced cell viability (p = 0.032), suggesting dose-dependent cytotoxicity.</div></div><div><h3>Conclusion</h3><div>Trehalose enhances neuronal differentiation and <em>VEGFA</em> secretion in hiPSC-NS/PCs, potentially augmenting the efficacy of transplantation therapy. These findings suggest that trehalose may serve as a valuable adjunct for neural regeneration, though optimal dosing must be determined to balance differentiation enhancement and cell viability. Further <em>in vivo</em> studies are warranted to validate its clinical applicability.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 268-277"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human iPSC-derived cerebral organoids reveal oxytocin-mediated protection against amyloid-β pathology","authors":"Tomoki Asaba,&nbsp;Sayuri Hamano,&nbsp;Ayaka Nanmo,&nbsp;Jieun Seo,&nbsp;Tatsuto Kageyama,&nbsp;Junji Fukuda","doi":"10.1016/j.reth.2025.06.013","DOIUrl":"10.1016/j.reth.2025.06.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuroinflammation is a key contributor to the pathogenesis of Alzheimer's disease (AD), and impaired clearance of amyloid-β (Aβ) by microglia is closely associated with disease progression. Oxytocin (OXT), a hypothalamic neuropeptide, has recently been reported to exert anti-inflammatory effects on microglia; however, its therapeutic potential in the human brain remains unclear.</div></div><div><h3>Methods</h3><div>We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) to model early AD-like pathology. Aβ toxicity was induced by applying 3 μM Aβ_1–42 for 48 h. The protective effects of OXT were evaluated through immunohistochemistry, RT-qPCR, calcium imaging, and multielectrode array (MEA) recordings. The involvement of microglia in Aβ clearance was assessed by immunostaining and gene expression analysis of TREM2.</div></div><div><h3>Results</h3><div>Aβ exposure led to significant deposition of Aβ in the outer layers of hCOs, accompanied by suppressed neural activity and increased apoptotic signaling. Pretreatment with OXT attenuated Aβ deposition and caspase-3-mediated apoptosis in a concentration-dependent manner. OXT also restored calcium oscillations and neuronal network activity as measured by MEA. Notably, OXT enhanced the recruitment of microglia to Aβ deposits and upregulated the expression of TREM2, a key regulator of microglial phagocytosis. Co-expression of oxytocin receptors (OXTR) on Iba1-positive microglia suggests that OXT directly modulates microglial activation and Aβ clearance.</div></div><div><h3>Conclusions</h3><div>OXT has neuroprotective effects on human cortical organoids by preserving their neuronal activity and promoting microglial-mediated Aβ clearance. This study provides novel insights into the therapeutic potential of OXT for targeting neuroinflammation and Aβ pathology in patients with AD.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 259-267"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects and the mechanism of pine pollen polysaccharides on diabetic wound healing in vitro and in vivo","authors":"Lan Chen ,&nbsp;Lifang Zhu ,&nbsp;Yu Cao","doi":"10.1016/j.reth.2025.06.009","DOIUrl":"10.1016/j.reth.2025.06.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Pine pollen polysaccharides (PPPS) has anti-inflammatory, immunomodulatory, anti-oxidant, hypoglycemic, and anti-bacterial properties. PPPS can accelerate wound healing in mouse cutaneous wounds, yet it is unclear whether PPPS can promote diabetic wound healing.</div></div><div><h3>Methods</h3><div>Fibroblasts, keratinocytes, and human umbilical vein endothelial cells (HUVECs) were stimulated with high glucose (HG) to mimic hyperglycemic environment. Cell viability, apoptosis, migration, and angiogenesis were assessed by cell counting, Western blot, transwell migration, and tube formation assays. Neutrophil extracellular traps (NETs) and macrophage polarization were analyzed by immunofluorescence and flow cytometry. Streptozotocin-induced diabetes mellitus (DM) mice were subjected to skin wounds and PPPS administration to validate the role of PPPS in diabetic wound healing.</div></div><div><h3>Results</h3><div>PPPS treatment impaired HG-induced viability reduction, apoptosis promotion, and migration repression of fibroblasts, keratinocytes, and HUVECs, accompanied by promotion of angiogenesis of HUVECs under HG stimulation. Specifically, PPPS treatment facilitated NET degradation and suppressed macrophage M1 polarization. Furthermore, PPPS accelerated diabetic wound healing in DM mice, along with decreased citrullinated H3 and PAD4 protein levels and elevated CD31 protein levels, suggesting that PPPS facilitated re-epithelialization and vascularization and reduced NETs.</div></div><div><h3>Conclusions</h3><div>PPPS accelerates diabetic wound healing via mediating NETs and the polarization of M1-type macrophages, providing new insights into the promoting role of PPPS in diabetic wound healing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 241-251"},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic Points to Consider for Cell Storage under the Act on the Safety of Regenerative Medicine in Japan","authors":"Yuki Uno ,&nbsp;Kazuaki Nakamura ,&nbsp;Morikuni Tobita ,&nbsp;Manabu Mizutani ,&nbsp;Masatoki Watanabe ,&nbsp;Kosuke Kawai ,&nbsp;Masahiro Kino-oka","doi":"10.1016/j.reth.2025.06.011","DOIUrl":"10.1016/j.reth.2025.06.011","url":null,"abstract":"<div><div>Regenerative medicine is an emerging field of medical treatment characterized by numerous uncertainties, necessitating regulatory frameworks that ensure both patient safety and timely clinical application. Among the three legislative measures established in Japan to facilitate the safety and efficient implementation of regenerative medicine, the Act on the Safety of Regenerative Medicine (RM Safety Act) governs regenerative medicine and cell therapies (RMTs) that utilize processed cells without manufacturing and marketing authorization. These therapies are conducted either as non-commercial clinical trials or as out-of-pocket therapies at the discretion of medical practitioners. More than a decade has passed since the enactment of the RM Safety Act, during which various aspects of RMTs have been clarified. The Evaluation Committee on Regenerative Medicine, Health Sciences Council, published the <em>Summary of the Review of the Act on the Safety of Regenerative Medicine, 5 Years After Its Enforcement</em>, which highlighted key challenges, including the lack of specific regulatory provisions for the storage of cells used in RMTs. In response, the Japanese Society for Regenerative Medicine developed the <em>Basic Points to Consider for Cell Storage under the Act on the Safety of Regenerative Medicine</em>, which outlines guidelines for practitioners intending to store human-derived, specified processed cells and/or their raw materials in a frozen state, as well as for institutions that provides cell storage. This review summarizes the current status and challenges of the RM Safety Act from the perspective of cell storage and provides an overview of the <em>Basic Points to Consider for Cell Storage under the Act on the Safety of Regenerative Medicine</em> and its role as an educational resource.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 252-258"},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mid-term outcomes of a bio-artificial pleura composed of autologous dermal fibroblasts used to close intraoperative pulmonary air leaks caused by intraoperative pleural injury: A case report","authors":"Masato Kanzaki ,&nbsp;Ryo Takagi ,&nbsp;Shota Mitsuboshi ,&nbsp;Tamami Isaka ,&nbsp;Masayuki Yamato","doi":"10.1016/j.reth.2025.06.001","DOIUrl":"10.1016/j.reth.2025.06.001","url":null,"abstract":"<div><h3>Introduction</h3><div>The visceral pleura is a thin, serous membrane that closely covers the surface of the lung. The pleura is injured or ruptured, causing air to accumulate in the thoracic cavity and the lung to collapse. Increased pleural pressure due to lung air leaks (LALs) from the lung can have serious effects. LALs are frequently observed due to pleural injury caused by lung resection. Postoperative LALs prolongs hospital stay and has a significant impact on patients' postoperative quality of life. Based on the above background, we developed and reported the effectiveness of dermal fibroblast sheet (DFS) as a bio-artificial pleura for closing LALs caused by intraoperative pleural injury in humans for the first time in a clinical study. There are no mid-term reports of bio-artificial pleura created using tissue engineering. In this study, we report the safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury in two cases.</div></div><div><h3>Previous study and case presentation</h3><div>Two of the five patients who met the criteria and underwent LAL closure using a bio-artificial pleura between May 2016 and March 2018 were followed up mid-term. Although the criteria included a 6-month monitoring period after LAL closure, these two patients continued to visit our hospital beyond the monitoring period for treatment of other comorbid conditions. Case 1. A male in his 40s who was receiving long-term steroid therapy for Takayasu's disease and underwent thoracoscopic lung wedge resection for a benign lung tumor in the left anteromedial basal segment. During surgery, the minor LALs from the resection margins with an automatic stapler were closed with a bio-artificial pleura, specifically, a total of three DFSs. During the patient's 51-month follow-up, no LAL recurrence, tumor development, infiltration, and fibrogenesis were observed. Case 2. A female patient in her 70s had bullae associated with combined pulmonary fibrosis and emphysema (CPFE). Thoracoscopic bullectomy of the left lower lobe was performed, and the major LALs were closed intraoperatively with a bio-artificial pleura consisting of a total of eight DFSs. She was readmitted for contralateral pneumonia 2 months after surgery. During a follow-up period of 82 months, no LAL recurrence and tumor development was observed in the operated left lung. However, chest CT revealed slowly progressing CPFE lesions.</div></div><div><h3>Conclusions</h3><div>This report of two cases demonstrated the mid-term safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 234-240"},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}