Regenerative Therapy最新文献

{"title":"Inhibition of the TLR4/RAGE pathway by clearance of extracellular HMGB1 is a potential therapeutic target for radiation-damaged salivary glands","authors":"Takashi I ,&nbsp;Riho Kanai ,&nbsp;Makoto Seki ,&nbsp;Hideki Agata ,&nbsp;Hideaki Kagami ,&nbsp;Hiroshi Murata ,&nbsp;Izumi Asahina ,&nbsp;Simon D. Tran ,&nbsp;Yoshinori Sumita","doi":"10.1016/j.reth.2025.07.004","DOIUrl":"10.1016/j.reth.2025.07.004","url":null,"abstract":"<div><h3>Introduction</h3><div>We recently developed a new therapy using effective-mononuclear cells (E-MNCs) and demonstrated its efficacy in treating radiation-damaged salivary glands (SGs). The activity of E-MNCs in part involves constituent immunoregulatory -CD11b/macrophage scavenger receptor 1(Msr1)-positive-M2 macrophages, which exert anti-inflammatory and tissue-regenerating effects via phagocytic clearance of extracellular high mobility group box 1 (HMGB1). Focusing on the phenomena, this study investigated significance of regulating the HMGB1/toll-like receptor 4 (TLR4)/receptor for advanced glycation end products (RAGE) signaling pathway in the treatment of SG dysfunction caused by radiation damage.</div></div><div><h3>Methods</h3><div>E-MNCs were transplanted into radiation-damaged mice SGs, and changes of TLR4/RAGE expression were observed. Furthermore, the activation of downstream signals was investigated in both intact SGs and cultured SG epithelial cells after irradiation. Subsequently, TLR4-knock-out (KO) mice were employed to examine how HMGB1/TLR4/RAGE signaling affected damage progression.</div></div><div><h3>Results</h3><div>Expression of both TLR4 and RAGE was diminished in ductal cells and macrophages/vascular endothelial cells of damaged SGs with E-MNC transplantation, respectively. Meanwhile, expression of TLR2/4 and RAGE in damaged SGs markedly increased in association with extracellular HMGB1 accumulation. Downstream signals were activated, and intranuclear localization of phospho-nuclear factor-kappa B (p–NF–KB) in ductal cells and production of IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were observed. Additionally, culture supernatant of irradiated cultured SG epithelial cells contained damaged associated molecular pattern (DAMP)/senescence-associated secretory phenotype (SASP) factors. Treatment of cultured SG epithelial cells with this supernatant activated TLR4 signaling pathway and induced cellular senescence. In TLR4-KO mice, onset of radiogenic SG dysfunction was markedly delayed. However, TLR2/RAGE signalings were alternatively activated, and SG function was impaired.</div></div><div><h3>Conclusions</h3><div>Clearance of DAMPs such as HMGB1 may attenuate sterile inflammation in damaged SGs via suppression of the TLR4/RAGE signaling pathway. This cellular mechanism may have significant implications for the development of future cell-based regenerative therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 476-490"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738556","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 growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair","authors":"Yang Shao ,&nbsp;Mei Han ,&nbsp;Guodong Song ,&nbsp;Cong Gao","doi":"10.1016/j.reth.2025.07.002","DOIUrl":"10.1016/j.reth.2025.07.002","url":null,"abstract":"<div><h3>Objective</h3><div>Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing.</div></div><div><h3>Methods</h3><div>ADSCs were isolated from adipose tissue, characterized via CD marker expression, and confirmed for multipotency using Oil Red O (adipogenesis), Alizarin Red S (osteogenesis), and Alcian Blue staining (chondrogenesis). ADSCs were then transduced with a lentiviral vector carrying HGH, generating HGH-ADSCs and confirmed by qRT-PCR. Fibroblasts (HDF-a) were co-cultured were co-cultured under HGH-ADSCs-conditioned medium and ADSCs-conditioned medium to assess proliferation (MTT assay), migration and invasion (Transwell), apoptosis (flow cytometry), and G0/G1 cell cycle progression. Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency. A burn rat model was established with three treatment groups: HGH-ADSCs, ADSCs, and saline. and histopathology (H&amp;E, TUNEL staining) analyzed epithelial regeneration and apoptosis. ELISA and biochemical assays quantified TNF-α, IL-1β, IL-6, MDA, SOD, and CAT in wound tissue homogenates.</div></div><div><h3>Results</h3><div>HGH-ADSCs significantly enhanced fibroblast proliferation, migration, invasion, and prolonged G0/G1 phase while reducing apoptosis (P &lt; 0.05). ERK inhibition abolished these effects (P &lt; 0.05). In vivo, HGH-ADSCs accelerated wound closure (P &lt; 0.05), enhanced epithelialization, reduced inflammation, and increased collagen formation. Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 465-475"},"PeriodicalIF":3.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724655","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":"A bibliometric analysis of the global status of platelet-rich plasma in regenerative medicine from 2004 to 2023","authors":"Siwen Zhang ,&nbsp;Xudong Zhang ,&nbsp;Haochen Zhang ,&nbsp;Shengqing Zhang ,&nbsp;Zichen Liu ,&nbsp;Shanshan Wu ,&nbsp;Yimeng Lu ,&nbsp;Chao Han ,&nbsp;Jichun Tan","doi":"10.1016/j.reth.2025.07.007","DOIUrl":"10.1016/j.reth.2025.07.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma (PRP) is a plasma product that concentrates platelets from whole blood and used widely in regenerative medicine. This study aimed to evaluate the evolution, development trend, and research highlights of research status of PRP in regenerative medicine.</div></div><div><h3>Methods</h3><div>Publications related to PRP were retrieved from the Science Citation Index Expanded (SCIE) database of the Web of Science (WoS) in February 2024. The impact factor (IF) was used to evaluate and compare the contributions of different countries. Then, the top 10 countries, top 10 productive journals, top 10 WoS categories, and top 10 most cited articles were listed. The data was processed, and the relative contributions of the top 10 productive countries in each year were presented in a line chart and a heatmap. VOSviewer software and heatmap were used to investigate the holistic trend of research highlights according to the change trends of keywords.</div></div><div><h3>Results</h3><div>A total of 9,577 publications were retrieved from SCIE database. The USA topped the list with 2,311 papers, followed by China (1,583 papers), the UK (525 papers), and Spain (512 papers). The studies of PRP in regenerative medicine have increasing trend globally. The USA had the most total citation and took the leading position for relative contributions, the UK ranked 1st in average citations and average IF. However, China's contribution had a dramatically increasing trend since 2015, and exceeded the USA in 2022. There were seven keywords of “Bone-related cluster”, “hyaluronic acid-related cluster”, “cartilage-related cluster”, “stomatology-related cluster”, “damage repair-related cluster”, “experiment-related cluster”, and “nerve-related cluster” generated in keyword co-occurrence analysis. Except for bone &amp; joint diseases, novel clinical applications of PRP have been carried out, including dental and neurological practice, reproductive medicine, dermatology, gynecology, and plastic surgery, cosmetic treatments, and the improvement of non-musculoskeletal organ function.</div></div><div><h3>Conclusion</h3><div>To summarize, the research advancements of PRP appear to be more prominent in the United States and China. Experimental research on PRP is mostly concentrated on exploring on mechanism and signal pathway. As an effective adjuvant treatment, the clinical application of PRP has expanded from initial trauma repair to multiple systemic organ disorders. Leveraging the intersection of multiple disciplines, the development of novel PRP-based medical materials tailored to specific disease characteristics may represent a promising direction for future research.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 456-464"},"PeriodicalIF":3.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724656","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":"Effectiveness of filling structures within nerve guidance conduits in a rat sciatic nerve injury model","authors":"Taisuke Kasuya ,&nbsp;Shunsuke Nishimoto ,&nbsp;Toru Iwahashi ,&nbsp;Junichi Sayanagi ,&nbsp;Yukio Hirai ,&nbsp;Toshiki Shimada ,&nbsp;Yoshiaki Yoshimura ,&nbsp;Katsuyuki Konishi ,&nbsp;Mai Konishi ,&nbsp;Ryoya Shiode ,&nbsp;Satoshi Miyamura ,&nbsp;Kunihiro Oka ,&nbsp;Tsuyoshi Murase ,&nbsp;Seiji Okada ,&nbsp;Hiroyuki Tanaka","doi":"10.1016/j.reth.2025.07.011","DOIUrl":"10.1016/j.reth.2025.07.011","url":null,"abstract":"<div><h3>Introduction</h3><div>The gold standard treatment for peripheral nerve gap injury is nerve autograft transplantation. Although various nerve guidance conduits (NGCs) have been developed as alternatives to autografting, few reports have evaluated the effects of the internal structure of NGCs on nerve regeneration. We investigated how the internal structure of NGCs affects nerve regeneration.</div></div><div><h3>Methods</h3><div>In 30 male Wistar rats, a 5 mm segment of the left sciatic nerve was resected, creating a gap. The animals were then randomly divided into two groups. A 7 mm polyglycolic acid (PGA) conduit, with (PGA-c group) or without a collagen filling (PGA group), was used to bridge the gap (n = 15 for each group). At 2 and 4 weeks postoperatively, longitudinal sciatic nerve slices were fluorescently immunostained with RECA-1 for endothelial cells, S100 for Schwann cells, and TUJ1 for axons. The fluorescence-positive areas were quantitatively evaluated. Next, 32 male Wistar rats underwent resection of a 10 mm segment of the left sciatic nerve. The animals were then assigned into four groups: sham group, autograft group, PGA-c group (transplantation of 12-mm PGA-c), and hollow PGA group (transplantation of 12 mm hollow PGA) (n = 8 for each group). At 12 weeks postoperatively, morphological evaluations and neurofunctional analyses were performed.</div></div><div><h3>Results</h3><div>In longitudinal sciatic nerve slices, the PGA-c group had significantly larger RECA-1-positive areas proximally and distally at 2 weeks, larger S100-positive areas proximally at 2 weeks, and larger TUJ1-positive areas proximally at 4 weeks postoperatively than the PGA group. In the 10 mm nerve defect model, the PGA-c group had a significantly higher percentage of myelinated axons, isometric tetanic force, and tibialis anterior muscle wet weight than the PGA group.</div></div><div><h3>Conclusions</h3><div>The internal filling structure of the NGCs may promote nerve regeneration by providing a scaffold for cells involved in nerve regeneration and may restore motor function. These findings provide new insights into the further structural development of NGCs suitable for peripheral nerve regeneration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 446-455"},"PeriodicalIF":3.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722033","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":"Mesenchymal stem cell application in Alzheimer's disease","authors":"Qianying Feng ,&nbsp;Fengxia Chen ,&nbsp;Rui Liu ,&nbsp;Dan Li ,&nbsp;Huigen Feng ,&nbsp;Junzheng Yang","doi":"10.1016/j.reth.2025.07.006","DOIUrl":"10.1016/j.reth.2025.07.006","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a type of degenerative disease that primarily affects in the central nervous system of elderly or pre-elderly individuals. The symptoms of Alzheimer's disease include memory impairment, aphasia, loss of function, dementia, and impairment of visual spatial ability, which in turn affects the physical health of patients. Mesenchymal stem cell therapy is a branch of regenerative medicine that primarily utilizes stem cells or their derivatives to stimulate the body's own healing process and repair damaged, diseased, or injured tissues. Its utilization in the treatment of autoimmune diseases and neurological disorders has been extensively documented. This review summarizes the preclinical and clinical applications of mesenchymal stem cells in AD, their underlying mechanisms and the application limitations of their application and potential solutions. It is hoped that researchers in this field will find it a useful foundation for further study of mesenchymal stem cell therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 439-445"},"PeriodicalIF":3.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713232","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":"Mesenchymal stem cells: A new strategy for the treatment of femoral head necrosis","authors":"Feng Tian ,&nbsp;Jiakang Peng ,&nbsp;Yongqing Xu ,&nbsp;Chuan Li","doi":"10.1016/j.reth.2025.07.008","DOIUrl":"10.1016/j.reth.2025.07.008","url":null,"abstract":"<div><div>Avascular necrosis of the femoral head (AVFH) is an orthopaedic disease triggered by ischaemic injury that is characterized by structural destruction of the femoral head and loss of function and severely affects the quality of life of patients. Currently, core decompression, bone grafting with vascularized tips, and artificial hip replacement are the main surgical treatment options used in clinical practice; however, these methods generally have limitations, such as trauma, high cost, and long postoperative recovery periods, which impose significant physiological and economic burdens on patients. In recent years, mesenchymal stem cells (MSCs) have shown great potential in the field of bone tissue engineering because of their unique biological properties. MSCs can self-renew and undergo multidirectional differentiation into osteoblasts, chondrocytes, and endothelial cells, and can also regulate the local microenvironment and promote the vascularization of the hip through the secretion of biologically active substances. MSCs can regulate the local microenvironment and promote new blood vessel and bone tissue regeneration through the secretion of growth factors, cytokines, and exosomes. The advantages of MSCs, such as easy access to materials, strong proliferation ability in vitro and stable osteogenic differentiation potential, make them ideal seed cells for femoral head necrosis treatment. However, ANFH treatment with MSCs faces many challenges: (1) the number of MSCs homing to lesion areas after intravenous infusion is limited; (2) the survival time and biological behaviour of locally injected MSCs are still unclear; (3) the mechanism of the interaction between MSCs and host cells has yet to be elucidated; and (4) efficiently modulating the microenvironment of necrotic areas for tissue regeneration needs to be investigated in depth. There are various innovative strategies to address these issues: enhancing the homing ability and in vivo stability of MSCs through genetic engineering; combining MSCs with biomaterials, such as hydrogels, to achieve precise targeting and slow release; and developing drug delivery systems for MSCs to improve therapeutic efficacy. In this paper, we systematically reviewed the pathological microenvironmental characteristics of femoral head necrosis and discuss the potential application, mechanism, existing problems, and solutions of MSCs in ANFH treatment in detail, providing a new theoretical basis and research direction for advancing the clinical treatment of femoral head necrosis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 421-429"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687177","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":"Evaluation of the usage of more than 50 sheets of autologous cultured epidermis (JACE®) sheets in treating patients with severe burns beyond insurance coverage limits","authors":"Yoshimi Yashiro ,&nbsp;Masukazu Inoie","doi":"10.1016/j.reth.2025.07.005","DOIUrl":"10.1016/j.reth.2025.07.005","url":null,"abstract":"<div><h3>Background</h3><div>Autologous cultured epidermis, JACE®, Japan's first regenerative medical product, is used as the standard treatment for wound closure in patients with severe burns. Although this product is listed for national health insurance in Japan, medical institutions place orders for JACE® beyond the limit of 50 sheets calculated for insurance coverage (insurance coverage limit) for lifesaving purposes. Therefore, the manufacturer and distributor continue to provide an excess amount, free from humanitarian considerations.</div></div><div><h3>Methods</h3><div>As a project supported by the Ministry of Economy, Trade, and Industry, the authors planned and conducted a non-interventional survey on the usage of JACE® from June 21, 2023, to February 29, 2024. In cases where more than 50 sheets of JACE® were used for patients with severe burns, information obtainable at the manufacturing stage and post-treatment feedback from physicians in charge were collected, and the requirement for JACE® were reviewed.</div></div><div><h3>Results</h3><div>During the survey period, interviews were conducted with physicians in charge at 30 institutions that placed orders for JACE® for the treatment of patients with severe burns. Of 43 patients, 13 received51 or more JACE® sheets. All were used at the request of the physician in charge and were confirmed to contribute to epithelialization, which closes burn wounds and saves lives. The mean age of the 13 patients who received 51 or more JACE® sheets (group H) was 53.2 years, which was lower than the63.1 years in the 30 patients who received 50 or fewer sheets (group L). The mean injured area was 55.9 % in group H and was clearly larger than the 37.0 % in group L. All patients with an injured area of 70 % or more were in group H, and three patients who received 100 or more JACE® sheets, with the highest reaching 165 sheets. In group H, JACE® tended to be used in younger patients with a large injured area and in elderly patients with a small injured area. A total of 434 sheets were provided to medical institutions free of charge to the 13 patients in group H.</div></div><div><h3>Conclusions</h3><div>Among the number of JACE® orders placed for the treatment of patients with severe burns, 30 % received more sheets than the insurance coverage limit; of the total number of sheets, 20.7 % were provided free of charge to medical institutions. Given this situation, the 50-sheet limit for insurance reimbursements need to be revisited.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 415-420"},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655445","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":"Culturing Potential: advances in ex vivo cell culture systems for haematopoietic cell-based regenerative therapies","authors":"Ayano Sugiyama-Finnis,&nbsp;Satoshi Yamazaki","doi":"10.1016/j.reth.2025.07.001","DOIUrl":"10.1016/j.reth.2025.07.001","url":null,"abstract":"<div><div>Stem-cell derived therapies are an essential pillar in the field of regenerative medicine, utilising stem cell self-renewal and multipotent or pluripotent differentiation capabilities to give rise to functional, specialised cells to repair and restore tissue function. Haematopoietic cell therapies have been pivotal to the development of the regenerative medicine field and continue to hold significant promise enabled by recent technical innovation in cell culture approaches that have expanded their therapeutic potential. The development of novel cell culture protocols that allow for the standardised ex vivo expansion of haematopoietic stem cells (HSCs) has facilitated the exploration of umbilical cord blood allogeneic HSC transplantation. Directed differentiation protocols of HSCs, embryonic stem cells and induced pluripotent stem cells, to selectively produce a desired haematopoietic cell type in a donor-independent manner, has broadened the scope for haematopoietic cell-based regenerative therapy. Furthermore, the integration of genome modification or gene editing with these protocols have allowed for corrective autologous HSC transplantation as well as the ability to confer haematopoietic cells with enhanced or novel therapeutic functions. Despite this, realising large-scale clinical translation remains challenging. Current efforts aim to move towards chemically defined culture systems, improving the efficiency and reproducibility of lineage-specific differentiation with an emphasis on compatibility with genome modification and gene-editing protocols for the scalable production of high-quality, efficacious and safe cellular therapies. In this review, we summarise the key milestones and technical advancements in the field in addition to the outstanding questions to be addressed.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 403-414"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655444","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":"Exosomes promise better bone regeneration","authors":"Shuaiwen Hu ,&nbsp;Shaogeng Wang ,&nbsp;Xiaomao Yang ,&nbsp;Ping Li ,&nbsp;Zhiguo Li ,&nbsp;Bin Luo ,&nbsp;Yujie Liang ,&nbsp;Xiaohua Pan","doi":"10.1016/j.reth.2025.06.020","DOIUrl":"10.1016/j.reth.2025.06.020","url":null,"abstract":"<div><div>Fractures primarily result from high-energy trauma, leading to structural discontinuity of bone tissue. Contemporary therapeutic approaches continue to face persistent challenges including nonunion, infection, and inflammatory complications that pose significant clinical management difficulties. Emerging evidence demonstrates that extracellular vesicles (EVs), particularly exosomes, serve as critical mediators in diverse pathophysiological processes. Accumulating studies reveal that exosomal cargos enhance osteogenesis and angiogenesis through dynamic regulation of cellular components and molecular networks within the bone remodeling microenvironment, thereby potentiating fracture healing cascades. This comprehensive review systematically examines the mechanistic contributions of exosomes in coordinating osteoblastic differentiation, osteoclastic activity modulation, and neovascularization processes. In addition, we describe the role of exosomes from different cellular sources (e.g., mesenchymal stem cells, endothelial progenitor cells, and osteoblasts) in fracture repair. Finally, this paper elaborates on the potential challenges and future directions for the development of novel exosome-based therapeutic strategies for clinical fracture repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 389-402"},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634298","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":"Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval","authors":"Kenichi Kimura ,&nbsp;Kojiro Imai ,&nbsp;Morio Ueno ,&nbsp;Chie Sotozono","doi":"10.1016/j.reth.2025.07.003","DOIUrl":"10.1016/j.reth.2025.07.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Recently, significant progress has been made in the field of regenerative medicine in Japan for the treatment of ophthalmic diseases, with a notable emphasis placed on clinical research and practical applications, and in 2014, one significant development was the initiation of the world's first clinical research using iPS cells for age-related macular degeneration. In addition, three regenerative medical products for the treatment of limbal stem cell deficiency, a rare and intractable ocular surface disease, have recently been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act). In order to expedite the practical implementation of regenerative medicine, the PMD Act presented a new category for regenerative medical products alongside the two categories that currently exist (i.e., 'pharmaceutical products' and 'medical devices'). However, within the current official Japanese national insurance coverage plan, there is no category designated for 'regenerative medical products'. Although the approval system for regenerative medical products differs from country to country (i.e., the United States Food and Drug Administration (U.S. FDA), the European Medicines Agency (EMA), etc.), in Japan, they are approved by the Japanese MHLW and PMDA. When manufacturers seek newly approved regenerative medical products in Japan to be incorporated within those listed in the Japanese national insurance coverage plan, the products are classified as either 'pharmaceutical products' or 'medical devices' and are reviewed by the Central Social Insurance Medical Council (\"Chuikyo\", in Japanese) of the Japanese MHLW. Although the responsibility for applying for regulatory approval and insurance coverage lies with the manufacturer, as the developer who conducted the clinical study and the investigator-initiated clinical trial for two ophthalmic regenerative medical products (i.e., Sakracy® and Vyznova®), we perceived that the period from regulatory approval to insurance coverage listing for these two products was longer than for other ophthalmic regenerative medical products. These experiences became the research question and the focus was on ophthalmic regenerative medical products, with the rationale behind this submission being that the dissemination of our experience will be of benefit to all clinical researchers and manufacturers. Hence, the purpose of this present study was to investigate the insurance coverage of regenerative medical products for ophthalmic diseases in Japan from the aspect of specific coverage-related categories.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, we investigated newly approved regenerative medical products for ophthalmic diseases in Japan after the Revised Pharmaceutical Affairs Act came into effect in 2014. The insurance coverage ","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 384-388"},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604785","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}