Regenerative Therapy最新文献

{"title":"Polydactyly bone marrow-derived mesenchymal stem cell-conditioned medium can prevent cartilage degeneration and alleviate knee pain in a rat model of osteoarthritis","authors":"Shunsuke Akai , Tomoya Iseki , Yoshitaka Nakao , Masakazu Toi , Tetsuto Yamaura , Shunsuke Takeuchi , Toshiya Tachibana","doi":"10.1016/j.reth.2025.07.010","DOIUrl":"10.1016/j.reth.2025.07.010","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is characterized by progressive degeneration of joint cartilage and has substantially increased worldwide. Recently, Mesenchymal stem cells (MSCs) have been explored as a cell-based therapy for the treatment of OA. MSC therapy has not been safely introduced into clinical practice due to immune rejection and the need for highly controlled culture protocols. The therapeutic efficacy of MSC treatment is mediated by the paracrine effect, and conditioned medium (CM) containing MSC-derived secreted factors have potential for useful cell-free therapy. CM can be prepared from various sources, though bone marrow MSCs obtained from infant polydactyly patients may be particularly useful for chondrogenic differentiation and the regulation of cartilage formation. The purpose of this study was to evaluate the effect of polydactyly bone marrow MSC-derived conditioned medium (pBMSC-CM) on the prevention of cartilage degeneration and knee pain using a rat monoiodoacetate (MIA)-induced knee OA model.</div></div><div><h3>Methods</h3><div>pBMSC-CM was isolated from the bone marrow of an infant polydactyly thumb. In vitro, cell proliferation was evaluated in chondrocytes cultured with pBMSC-CM, and gene expression of cartilage matrix markers was assessed by quantitative reverse transcription PCR. RNA sequencing was conducted to analyze differentially expressed genes in pBMSCs. A knee arthritis model was generated by an intra-articular injection of MIA into the right knee of 18 Sprague-Dawley rats, which were then divided into three groups: (1) No-treatment group, (2) Culture medium only group, and (3) pBMSC-CM group. Each group received intra-articular injections of either saline, alpha-Minimal Essential Medium, or pBMSC-CM one week after the MIA injection. To assess knee joint pain, the struggle threshold of the knee joint extension angle was measured every week. Two weeks after treatment injections, a retrograde neurotracer was injected into both knees. After one week, articular cartilage and synovitis were evaluated based on histological characteristics. The dorsal root ganglions (DRG) were immunostained to evaluate the expression of calcitonin gene-related peptide (CGRP).</div></div><div><h3>Results</h3><div>pBMSC-CM enhanced chondrocyte proliferation and upregulated cartilage matrix genes. Chondrogenic and neuroprotective genes were highly expressed in pBMSCs. In behavioral tests, the pBMSC-CM group showed significant improvement in struggle threshold compared to the no-treatment and culture medium only groups. Histological evaluation showed significantly less cartilage degeneration in the pBMSC-CM group than in the other two groups. There were no significant differences in the degree of synovitis among the three groups, although CGRP expression in DRG was lower in the pBMSC-CM group.</div></div><div><h3>Conclusion</h3><div>In this study, pBMSC-CM therapy reduced extracellular matrix degeneration in the articular ","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 525-534"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772687","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":"Scalable production process development for NK cells targeting large-scale expansion","authors":"Takuya Kikuchi,&nbsp;Ippei Takeuchi,&nbsp;Hideto Yamaguchi","doi":"10.1016/j.reth.2025.07.014","DOIUrl":"10.1016/j.reth.2025.07.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Natural Killer (NK) cells have attracted extensive attention as therapeutic agents for hematological malignancies and solid tumors. NK cell therapies carry a lower risk of Graft-Versus-Host Disease (GVHD) in allogeneic transplantation, making them ideal candidates for “off-the-shelf” allogeneic cell therapies. However, the expansion culture of NK cells typically employs a scale-out strategy using a large number of culture vessels, making it still challenging to use NK cells as 'off-the-shelf' allogeneic cell therapies. While scalable, aerated stirred bioreactor could be an ideal approach, there have been no reports on culture evaluations specifically targeting iPCS-derived NK cells.</div></div><div><h3>Methods</h3><div>We developed a process for expanding iPCS-derived NK cells using a stirred culture system. The NK cell stimulation process with agonist antibodies and expansion process were repeated, and the cell expansion and quality of iPCS-derived NK cells were evaluated. Scale-up factors were evaluated using an aerated stirred bioreactor, and process scale-up was performed from 1 L to 10 L bioreactors.</div></div><div><h3>Results</h3><div>iPCS-derived NK cells showed higher cell expansion in stirred cultures than in static cultures. By repeated stimulation and expansion processes, iPCS-derived NK cells expanded 1000-fold with comparable cell expansion and quality. iPCS-derived NK cells could be scaled up from 1 L to 10 L aerated stirred bioreactors with comparable cell expansion and quality.</div></div><div><h3>Conclusions</h3><div>Through systematic process evaluation and optimization, we demonstrated that iPCS-derived NK cells can be expanded in a scalable aerated stirred bioreactor.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 535-543"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780153","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":"Subretinal suspensions of hiPSC-derived retinal pigment epithelium cells form functional monolayers in NOD-SCID mice facilitating treatment of advanced retinal diseases","authors":"Xiaojing Song ,&nbsp;Guanjie Gao ,&nbsp;Ke Ye,&nbsp;Ping Xu,&nbsp;Yuan Wang,&nbsp;Suai Zhang,&nbsp;Dandan Zheng,&nbsp;Jian Ge,&nbsp;Xiufeng Zhong","doi":"10.1016/j.reth.2025.06.021","DOIUrl":"10.1016/j.reth.2025.06.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Transplantation of human induced pluripotent stem cells derived retinal pigment epithelium (hiPSC-RPE) is regarded as one of the most promising strategies for advanced retinal degenerative diseases leading to blindness, such as age-related macular degeneration. Despite its therapeutic potential, this approach is encumbered by critical challenges, notably the survival of donor RPE cells post-transplantation and the successful reconstruction of a functional RPE layer.</div></div><div><h3>Methods</h3><div>With our previously reported strategy, abundant hiPSC-RPEs were generated from human induced pluripotent stem cells. These cells were characterized <em>in vitro</em> by morphology, marker expression and function. Further, hiPSC-RPE cell suspensions were injected into the eyes of NOD-SCID mice. Animals were monitored by optical coherence tomography screening and color fundus imaging to evaluate the survival of hiPSC-RPEs. Polarity, maturity, integration and phagocytosis of hiPSC-RPEs were analyzed histologically.</div></div><div><h3>Results</h3><div>hiPSC-RPE cells exhibited a cobblestone morphology with abundant microvilli and tight junctions, expressed RPE specific molecular markers, and possessed ability to phagocytize photoreceptor outer segments (POS), thereby resembling the characteristics of the native human RPE cells. Following transplantation into NOD-SCID mice, the cells survived for the 8-week testing period and formed a highly organized monolayer in regions with an intact Bruch's membrane (BM) in the host retina. The reconstructed RPE layer expressed both human-specific and RPE-specific markers with POS phagocytic function. No severe adverse effects, such as malignant tumors or infections, were observed.</div></div><div><h3>Conclusions</h3><div>These findings demonstrate that hiPSC-RPE suspensions can survive and form RPE monolayers with morphological and functional features analogous to those of native human RPE cells in the host retina with a healthy BM. Our study may facilitate the development of cell-based therapies for treatment of advanced retinal degenerations.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 503-514"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772685","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":"Rat adipose-derived mesenchymal stem cell-derived exosomes loaded with miR-375 promote neurite outgrowth and peripheral nerve regeneration via activation of Akt by targeting EPHA4","authors":"Zhiwei Liu,&nbsp;Yuanyuan Han,&nbsp;Chunjie Song","doi":"10.1016/j.reth.2025.06.010","DOIUrl":"10.1016/j.reth.2025.06.010","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs (miRNAs) carried by mesenchymal stem cells (MSCs)-derived exosomes participate in peripheral nerve regeneration. Our study intended to determine the role of miR-375-loaded exosomes secreted by adipose-derived MSCs (ADMSCs) in dorsal root ganglion (DRG) neurons <em>in vitro</em> and in rat models of sciatic nerve injury as well as the underlying mechanisms.</div></div><div><h3>Methods</h3><div>After the isolation of primary rat ADMSCs and DRG neurons, the characteristics of ADMSC-derived exosomes were identified by western blotting and nanoparticle tracking analysis. MiR-375 mimics or NC mimics were transfected into ADMSCs to prepare exo-miR-375 or exo-NC. Then, DRG neurons were co-cultured with exo-miR-375 or exo-NC to analyze the influence of exosomes loaded with miR-375 on axon extension by neurofilament immunofluorescence staining and neurotrophic factor production by RT-qPCR. A walking track analysis was conducted to assess the effects of exo-miR-375 or exo-NC injection on the recovery of rat sciatic nerve functions. Axon and myelinated fiber regeneration in injured nerves was observed through toluidine blue staining, transmission electron microscopy (TEM), and neurofilament immunofluorescence staining. TargetScan and miRDB databases were used to screen for miR-375 downstream target genes. The miR-375 and EPHA4 interaction relationship was validated through dual luciferase reporter assay. The phosphorylation of Akt in sciatic nerve tissues was determined via western blotting.</div></div><div><h3>Results</h3><div>ADMSCs-derived exosomes with overexpressed miR-375 stimulated axon extension and enhanced neurotrophic factor expression in DRG neurons as well as improved limb function recovery, facilitated axon myelinated fiber regeneration, and alleviated gastrocnemius muscle atrophy in rats after sciatic nerve injury. EPHA4 targeted by miR-375. Overexpressing EPHA4 reversed the promotion of exo-miR-375 on neurite outgrowth <em>in vitro</em>. Additionally, exo-miR-375 significantly reduced EPHA4 levels but elevated phosphorylated-Akt levels in rat sciatic nerves.</div></div><div><h3>Conclusion</h3><div>ADMSCs-derived exosomes with overexpressed miR-375 promoted neurite outgrowth and peripheral nerve regeneration by activating Akt through downregulating EPHA4.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 491-502"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772702","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":"Development of rematuration of canine chemically induced hepatic progenitor cells using 3D rocking culture","authors":"Kaoruko Kikuchi ,&nbsp;Yoko Yamada ,&nbsp;Sakurako Neo ,&nbsp;Suguru Nitta ,&nbsp;Hirotaka Igarashi ,&nbsp;Akihide Kamiya ,&nbsp;Masaharu Hisasue","doi":"10.1016/j.reth.2025.06.002","DOIUrl":"10.1016/j.reth.2025.06.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Developing canine hepatocyte culture systems is critical for liver transplantation, toxicity evaluation, and drug metabolism studies. However, maintaining viable and functional hepatocytes in long-term cultures remains challenging. Our prior research demonstrated differentiation of cryopreserved canine hepatocytes into hepatic progenitor cells (cHPCs) using three small-molecule compounds: Y-27632 (ROCK inhibitor), A-83-01 (TGFβ inhibitor), and CHIR99021 (GSK3 inhibitor). Nevertheless, rematuration into functional hepatocytes was not achieved. This study aimed to evaluate the differentiation of progenitor cells into mature hepatocytes, compare two-dimensional (2D) and three-dimensional (3D) culture systems, and determine the advantages of 3D culture.</div></div><div><h3>Methods</h3><div>cHPCs were cultured in 2D cultures with HGF and oncostatin M or in 3D cultures using AggreWell400^TM plates to form spheroids, transferred to low-adherent plates, and cultured with shaking. Cells were analyzed for morphology, gene expression, and protein markers using immunocytochemistry.</div></div><div><h3>Results</h3><div>In 2D cultures, rematuration produced cells with wider cytoplasm, multiple nuclei, and a paving stone–like morphology. Spheroids in 3D cultures reached 150 μm in diameter with irregular edges by day 5. Quantitative real-time polymerase chain reaction analysis revealed significant upregulation of liver-specific genes. In 2D cultures, <em>KRT19</em> expression increased 1.7-fold compared with cHPCs(<em>p</em> &lt; 0.01). In 3D cultures, <em>ALB</em> (63-fold), <em>TAT</em> (9-fold), <em>MRP2</em> (34-fold), <em>EpCAM</em> (1.6-fold), <em>CYP2E1</em> (10-fold), and <em>CYP3A12</em> (56-fold) were all significantly upregulated compared with cHPCs (<em>p</em> &lt; 0.05). Immunohistochemistry showed robust AFP, ALB, and CYP2E1 expression in 3D cultures, with 87.6 % of cells AFP-positive and 100 % CYP2E1-positive compared to 11.4 % and 7.9 % in 2D cultures, respectively.</div></div><div><h3>Conclusions</h3><div>3D rocking culture markedly enhanced liver-specific gene and protein expression, producing functional liver spheroids. These findings underscore the potential of 3D rocking cultures to create reliable, <em>in vivo</em>–like liver models for research and therapeutic applications.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 430-438"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772701","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":"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}