Regenerative Therapy最新文献

{"title":"Best evidence summary for platelet-rich plasma treatment of chronic wounds","authors":"Xinru Zhang ,&nbsp;Xingxing Zhang ,&nbsp;Luxin Wang ,&nbsp;Li Zhen ,&nbsp;Meiyan Lin ,&nbsp;Yanan Li ,&nbsp;Lihong Gong ,&nbsp;Haiting Zeng ,&nbsp;Weiqing Ruan ,&nbsp;Mulan Zhu","doi":"10.1016/j.reth.2025.101053","DOIUrl":"10.1016/j.reth.2025.101053","url":null,"abstract":"<div><h3>Objective</h3><div>To summarize the best evidence for platelet-rich plasma therapy in chronic wounds, providing an evidence-based foundation for standardizing its clinical practice.</div></div><div><h3>Methods</h3><div>Guided by the “6S” evidence pyramid model, we systematically searched 12 databases including Cochrane Library and Pubmed, 9 guideline websites including Guidelines International Network (GIN) and National Institute for Health and Clinical Excellence (NICE), and 10 professional websites including World Union of Wound Healing Societies (WUWHS), for relevant evidence from the establishment of the database to May 1, 2025. Two researchers independently conducted quality assessment, evidence extraction, and integration of the included literature.</div></div><div><h3>Results</h3><div>A total of 17 articles were included, comprising 3 guidelines, 5 expert consensus statements, and 9 systematic reviews. The evidence was categorized into six key treatment domains: application principles, indications and contraindications, pre-treatment preparations, treatment protocols, efficacy monitoring, and management strategies. 27 individual recommendations were derived from these categories.</div></div><div><h3>Conclusion</h3><div>Platelet-rich plasma therapy can be used as an adjunctive treatment for the management of chronic wounds. Clinicians and wound care specialists should thoroughly assess the applicability and timing of platelet-rich plasma, considering the specific clinical context, and combine it with the patient's physical condition and preferences for clinical application, promoting chronic wound healing and reducing the global disease burden of chronic wounds.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101053"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839202","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":"Decellularized corneal-based 3D scaffolds: methods decellularization, characterization, mechanical properties, and species source","authors":"Vahid Akbaripour ,&nbsp;Leila Rezaei ,&nbsp;Gelavizh Rostaminasab ,&nbsp;Farid Daneshgar ,&nbsp;Omid Bahiraee ,&nbsp;Leila Rezakhani","doi":"10.1016/j.reth.2025.101044","DOIUrl":"10.1016/j.reth.2025.101044","url":null,"abstract":"<div><div>Corneal blindness is a significant worldwide health issue owing to low number of global corneal donors. Decellularized corneal scaffolds intend to be a promising choice for corneal repair by maintaining the native extracellular matrix (ECM) while minimizing immune reactions. This effort comprehensively reviews various decellularization strategies such as physical, chemical, and biological methods and their impact on ECM integrity, transparency, and mechanical strength. We explored source tissues such as porcine, human, and SMILE-derived lenticules based on their structure similarity and clinical suitability. Characterization techniques including immunohistochemical, histological, mechanical, and in vivo assessments are reviewed to evaluate scaffold quality and biocompatibility. Recellularization approaches which restore corneal functionality, using epithelial, stromal, and endothelial cells also have been investigated. Additionally, progresses in composite biomaterials and 3D bioprinting utilizing decellularized corneal matrices are highlighted, showing enhanced transparency, adhesion, and regenerative potential. Despite clinical progress which is evidenced by successful preclinical studies and clinical trials, some challenges such as protocols optimization, large-scale production, and integration with host tissue remain. Further integrated research is essential to optimize scaffold design, ensure long-term safety, and establish decellularized corneas as a possible solution to the scarcity of donor tissues for transplantation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101044"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578353","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":"Sustained release of quercetin through homogeneous poly (lactic-co-glycolic acid) microspheres to enhance MSCs biofunctions for regenerative therapy","authors":"Xianghui Mei ,&nbsp;Dongchao Li ,&nbsp;Li Sun ,&nbsp;Zhen Wang ,&nbsp;Houjian Ren ,&nbsp;Hui Zhang ,&nbsp;Min Ge ,&nbsp;Defeng Wang ,&nbsp;Qizhi Shuai","doi":"10.1016/j.reth.2026.101085","DOIUrl":"10.1016/j.reth.2026.101085","url":null,"abstract":"<div><h3>Introduction</h3><div>Mesenchymal stem cells (MSCs) hold significant potential for tissue repair and cell therapy. A primary obstacle in their application is the loss of stemness and onset of senescence during in vitro expansion, which compromises therapeutic efficacy. Plant-derived bioactive compounds like quercetin (Que) offer promise for enhancing MSC-based therapies; however, its poor aqueous solubility due to high lipophilicity and phenolic hydroxyl groups limits pharmaceutical utility.</div></div><div><h3>Methods</h3><div>To address this, we engineered homogeneous poly(lactic-co-glycolic acid) (PLGA) microspheres (hPLGA-Ms) using microfluidic technology to encapsulate hydrophobic Que, enabling its sustained release in physiological aqueous environments.</div></div><div><h3>Results</h3><div>The results showed the hPLGA-Ms loaded Que (Que/hPLGA-Ms) were uniform, well dispersed. The size of the hPLGA-Ms can be precisely controlled by adjusting the flow rates of two phases. Gene expression analysis demonstrated the hPLGA-Ms delivery of Que enhanced MSCs cellular viability, stemness, anti-senescence, secretion and migration abilities of cells.</div></div><div><h3>Conclusions</h3><div>In summary, the scalable and reproducible Que/hPLGA-Ms provide controlled release kinetics and significantly potentiate MSCs bioactivities. This delivery system represents a promising strategy for tissue engineering and regenerative therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101085"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420277","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":"Role of WIF-1 in regulating chondrocyte dedifferentiation and matrix production through WNT pathway","authors":"Yu-Ying Chu ,&nbsp;Yukiyo Asawa ,&nbsp;Naoki Tsuji ,&nbsp;Tomoaki Sakamoto ,&nbsp;Dan Liu ,&nbsp;Kazuto Hoshi ,&nbsp;Atsuhiko Hikita","doi":"10.1016/j.reth.2026.101083","DOIUrl":"10.1016/j.reth.2026.101083","url":null,"abstract":"<div><h3>Introduction</h3><div>Chondrocyte dedifferentiation during monolayer expansion is a major barrier to producing clinically reliable cells for cartilage regeneration. The upstream regulators governing this phenotypic instability are not fully defined. This study identifies WNT inhibitory factor 1 (WIF1) as a potential key molecular determinant of chondrocyte stability.</div></div><div><h3>Methods</h3><div>Human auricular chondrocytes (HACs) were expanded to early (P2) and late (P7) passages. Transcriptomic profiling, qPCR, GAG quantification, and histology were performed in 2D monolayer and 3D atelocollagen pellet cultures. WIF1 function was interrogated using lentiviral knockdown and overexpression. β-catenin, <em>p</em>-SMAD2/3, <em>p</em>-JNK, COL1A1, COL2A1, and WIF1 were evaluated by immunohistochemistry.</div></div><div><h3>Results</h3><div>Late-passage HACs showed marked dedifferentiation, including reduced WIF1, COL2A1, ACAN, and SOX9 with concomitant increases in COL1A1, ACTA2, and MMP9. WIF1 knockdown in early-passage cells reproduced this phenotype, inducing β-catenin nuclear accumulation, increased SMAD2/3 and JNK activation, diminished GAG synthesis, and loss of cartilage-specific ECM architecture. Conversely, WIF1 overexpression in P7 chondrocytes restored chondrogenic markers, enhanced proteoglycan-rich ECM formation, and suppressed fibroblastic gene expression. WIF1 overexpression re-established a signaling profile resembling early-passage cells, characterized by low β-catenin, reduced <em>p</em>-SMAD2/3, and attenuated <em>p</em>-JNK.</div></div><div><h3>Conclusions</h3><div>WIF1 functions as a critical upstream regulator that maintains chondrocyte identity by simultaneously suppressing WNT/β-catenin, TGF-β/SMAD, and JNK stress signaling. Its loss is a hallmark of dedifferentiation, while its restoration reverses transcriptional drift and rescues ECM-producing capacity. These findings highlight WIF1 as a promising therapeutic target to improve the stability of expanded chondrocytes and enhance the quality of regenerative cartilage constructs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101083"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420278","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":"Efficacy and safety of autologous adipose-derived stem cells combined with platelet-rich plasma for periodontal regeneration: a multicenter, randomized, open-label, parallel-group comparative trial","authors":"Morikuni Tobita ,&nbsp;Yosuke Masubuchi ,&nbsp;Yorimasa Ogata ,&nbsp;Akio Mitani ,&nbsp;Takeshi Kikuchi ,&nbsp;Jun-Ichiro Hayashi ,&nbsp;Taku Toriumi ,&nbsp;Anna Arita ,&nbsp;Jorge Luis Montenegro Raudales ,&nbsp;Hiroshi Mizuno ,&nbsp;Yuki Suzuki ,&nbsp;Keiko Wakana ,&nbsp;Hikari Yoneda ,&nbsp;Masahiro Kino-oka ,&nbsp;Tomohiro Morio ,&nbsp;Kiyoshi Okada ,&nbsp;Shinya Murakami ,&nbsp;Masaki Honda","doi":"10.1016/j.reth.2026.101062","DOIUrl":"10.1016/j.reth.2026.101062","url":null,"abstract":"<div><h3>Introduction</h3><div>Periodontitis is a chronic inflammatory disease caused by dental biofilm that destroys the periodontal tissues supporting the teeth. We aimed to evaluate the efficacy and safety of co-transplantation of autologous adipose-derived mesenchymal stem cells (ASCs) with platelet-rich plasma (PRP) compared to enamel matrix derivative (EMD) for regenerating periodontal tissue damaged by chronic periodontitis.</div></div><div><h3>Methods</h3><div>In this multicenter, randomized, open-label, parallel-group phase II therapeutic equivalence trial, we assessed the effects of ASCs with PRP versus EMD on alveolar bone height and width, as well as other periodontal indices. Measurements of primary and secondary endpoints and periodontal tissue indices were performed at baseline, the day of transplantation, and at 12, 24, and 36 weeks post-transplantation. Data were analyzed using Student's t-test.</div></div><div><h3>Results</h3><div>Of the 21 patients initially recruited, 9 in the ASCs + PRP group and 6 in the EMD group completed the study. The ASCs + PRP treatment demonstrated greater regenerative potential than that of EMD, with a significantly higher alveolar bone height at 36 weeks post-treatment. Patients receiving ASCs + PRP treatment showed a statistically higher mean height of new alveolar bone in the transplanted area than those in the EMD group. Clinical attachment levels improved significantly from baseline at 12, 24, and 36 weeks in the ASCs + PRP group; however, no significant difference in clinical attachment gain was observed between the two groups. Adverse events in the ASCs + PRP group were neither related to the implantation site nor to the treatment.</div></div><div><h3>Conclusions</h3><div>Co-transplantation of ASCs with PRP is a safe and effective approach for periodontal regeneration, offering a promising therapeutic strategy for the treatment of periodontitis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101062"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976703","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":"Extracellular vesicles derived from adipose-derived mesenchymal stem/stromal cells prevent synovial inflammation and attenuate cartilage degeneration in rodent osteoarthritis","authors":"Yushi Maruiwa ,&nbsp;Yasuo Niki ,&nbsp;Yo Mabuchi ,&nbsp;Osamu Takeuchi ,&nbsp;Satoshi Kuronuma ,&nbsp;Yoshitsugu Fukuda ,&nbsp;Atsuhiro Fujie ,&nbsp;Akihito Oya ,&nbsp;Shu Kobayashi ,&nbsp;Masaya Nakamura","doi":"10.1016/j.reth.2025.101056","DOIUrl":"10.1016/j.reth.2025.101056","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is the most common joint disease in the elderly and a major cause of pain and disability. Recent advances in OA therapy have led to a greater variety of treatment options. Extracellular vesicles (EVs) have recently emerged as a potential therapeutic approach for OA. This study aimed to demonstrate the disease-modifying effects of adipose-derived mesenchymal stem cell-derived EVs (MSC-EVs) on OA.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effects of MSC-EVs were evaluated using RAW264.7 macrophage-like cells stimulated with lipopolysaccharide and human synovial cells stimulated with IL-1β. In vivo, MSC-EVs were administered intra-articularly into knees of rats with monosodium iodoacetate (MIA)-induced OA. Pain thresholds, gait parameters, histological scores, and cytokine levels were assessed. Single-cell RNA sequencing (scRNA-seq) was performed on joint tissues to evaluate cell-specific gene expression and macrophage polarization.</div></div><div><h3>Results</h3><div>In vitro, MSC-EVs reduced the mRNA expression of IL-1β and IL-6 in RAW264.7 cells, and significantly suppressed multiple inflammatory cytokines while upregulating FGF-18 in synovial cells. In vivo, intra-articular MSC-EV injection increased pain threshold, improved gait, and reduced synovial inflammation and cartilage degeneration. scRNA-seq revealed decreased inflammatory cytokines, increased PRG4 and FGF-18 expression, and a shift in macrophage polarization toward an M2 phenotype in the EV-treated group.</div></div><div><h3>Conclusion</h3><div>MSC-EVs exert anti-inflammatory and cartilage-protective effects in OA through immune modulation and regenerative signaling, indicating their significant therapeutic potential as a disease-modifying strategy for OA.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101056"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883644","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":"First-in-human study to investigate the safety and efficacy of effective-mononuclear cell therapy for radiogenic xerostomia","authors":"Takashi I ,&nbsp;Mayumi Iwatake ,&nbsp;Takako Yoshida ,&nbsp;Kazuhiro Nagai ,&nbsp;Yuka Hotokezaka ,&nbsp;Mika Nishihara ,&nbsp;Ryo Honma ,&nbsp;Hiroshi Harada ,&nbsp;Munehiro Hayashida ,&nbsp;Toshiki Nagano ,&nbsp;Riho Kanai ,&nbsp;Seigo Ohba ,&nbsp;Atsutoshi Yoshimura ,&nbsp;Haruchika Masuda ,&nbsp;Takayuki Asahara ,&nbsp;Yasushi Miyazaki ,&nbsp;Atsushi Kawakami ,&nbsp;Izumi Asahina ,&nbsp;Makoto Seki ,&nbsp;Yoshinori Sumita","doi":"10.1016/j.reth.2025.101059","DOIUrl":"10.1016/j.reth.2025.101059","url":null,"abstract":"<div><h3>Background</h3><div>Salivary gland (SG) hypofunction is the most common complication following radiotherapy for head and neck cancer. Currently, there are no effective therapies for radiation-induced xerostomia. We recently developed a novel therapy for preclinical studies using effective-mononuclear cells (E-MNCs) induced from autologous peripheral blood mononuclear cells (PB-MNCs) via a new primary culture system for treatment of radiation-induced xerostomia. However, the safety and effectiveness of E-MNC therapy have not been assessed in humans. The objective of this first-in-human study was to evaluate the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia.</div></div><div><h3>Methods</h3><div>This first-in-human study was an open-label, single-center, two-step dose escalation study. A total of 5 patients who had no recurrence of head and neck cancer over a 5-year period following radiation therapy and suffered from radiation-induced xerostomia received a transplantation of E-MNCs to one-sided submandibular gland (SMG). The primary endpoint was the safety of the protocol. The secondary endpoint was effectiveness evaluated based on change from baseline in whole-saliva secretion, MRI/CT-evaluated volume of the SMG and subjective/objective symptoms after intervention. The duration of the intervention was 1 year.</div></div><div><h3>Results</h3><div>During follow-up, no treatment-related adverse events were detected. The stimulated whole salivary flow rate increased from an average of 3.86 mL/10 min at baseline to 5.16 mL/10 min at 6 months post–investigational intervention. Additionally, subjective/objective symptoms improved in 4 of 5 treated patients. By contrast, imaging findings revealed no obvious changes in MRI/CT-evaluated volume of SMGs due to conspicuous progression of atrophy and fibrosis compared with baseline.</div></div><div><h3>Conclusion</h3><div>This is the first clinical study to evaluate the safety and efficacy of E-MNC treatment in patients with severe radiation-induced xerostomia. The results of our study indicate that E-MNC treatment is safe and effective, and provide valuable information that will aid in designing subsequent clinical studies.</div></div><div><h3>Trial registration</h3><div>This study was registered with the Japan Registry of Clinical Trials (<span><span>http://jrct.niph.go.jp</span><svg><path></path></svg></span>) as jRCTb070190057.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101059"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924579","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":"Immune synapse molecules knockout in induced pluripotent stem cells enables broad NK cell resistance in T cell progeny","authors":"Jing Zhang ,&nbsp;Keisuke Sumide ,&nbsp;Keitaro Kanie ,&nbsp;Akihiro Ishikawa ,&nbsp;Munehiro Yoshida ,&nbsp;Tomoko Ishii ,&nbsp;Bo Wang ,&nbsp;Shin Kaneko","doi":"10.1016/j.reth.2026.101060","DOIUrl":"10.1016/j.reth.2026.101060","url":null,"abstract":"<div><h3>Introduction</h3><div>Allogeneic iPSCs provide a potential source for regenerative T cell therapies, yet their clinical application remains limited by immune rejection driven by human leukocyte antigen (HLA) incompatibility. Knockout of β2-microglobulin (B2M) eliminates HLA class I expression and protects against CD8⁺ T cell-mediated killing, but paradoxically provokes natural killer (NK) cell activation via the “missing-self” response. Existing approaches seek to enhance inhibitory signaling or dampen activating signals, yet these approaches achieve only partial NK evasion due to the extraordinary heterogeneity of NK receptor repertoires.</div></div><div><h3>Methods</h3><div>We developed a broader and more universal immune evasion strategy by targeting immune synapse (IS) adhesion molecules that critical for NK–target cell engagement. Building on our previously reported hypoimmunogenic iPSC-derived T cell (iT cell) platform (B2M^KOCIITA^KOPVR^KO with HLA-E overexpression), we engineered double-knockout (dKO) iT cells lacking CD54 (ICAM-1) and CD58 (LFA-3) using CRISPR/Cas9-mediated gene editing. These two ligands play key roles in stabilizing NK–target immunological synapses.</div></div><div><h3>Results</h3><div>Functionally, dKO iT cells exhibited marked resistance to NK cell–mediated cytotoxicity both in vitro and in vivo in human IL-15 transgenic mouse model, while maintaining iT cell cytotoxic effector functions. By disrupting the physical interface required for NK engagement, this approach provides broad protection against diverse NK cell subsets and complements existing HLA-focused immune evasion strategies.</div></div><div><h3>Conclusions</h3><div>Our findings establish a potentially versatile platform for generating universal, NK-resistant iT cells and advance the translational potential of iPSC-based immunotherapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101060"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976704","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":"Stable and functional regulatory T cell attenuates fibrotic remodeling in heart failure","authors":"Takura Taguchi ,&nbsp;Takuji Kawamura ,&nbsp;Norihisa Mikami ,&nbsp;Kosuke Torigata ,&nbsp;Akima Harada ,&nbsp;Lisa Fujimura ,&nbsp;Emiko Ito ,&nbsp;Maki Takeda ,&nbsp;Kenji Miki ,&nbsp;Shimon Sakaguchi ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2026.101079","DOIUrl":"10.1016/j.reth.2026.101079","url":null,"abstract":"<div><h3>Introduction</h3><div>Heart failure involves myocardial fibrosis and impaired cardiac function. The transverse aortic constriction (TAC) model in mice replicates pressure overload-induced fibrosis. Immune-mediated inflammation, particularly through T lymphocytes and macrophages, plays a pivotal role in the progression of fibrosis. In vitro–induced regulatory T cells (Tregs) are limited by Foxp3 instability. To address this, stable and functional in vitro induced Tregs (S/F-iTregs) have been developed under CD28-deprived conditions, exhibiting sustained Foxp3 expression and epigenetic stability. We aimed to evaluate the therapeutic efficacy of intravenously administered S/F-iTregs in a murine TAC model of heart failure.</div></div><div><h3>Methods</h3><div>S/F-iTregs were generated from CD4⁺ conventional T cells under CD28 costimulation-deficient conditions. BALB/c mice underwent TAC surgery and received S/F-iTregs intravenously. Cardiac function was assessed by echocardiography. Myocardial fibrosis was evaluated using histological staining. Bulk RNA sequencing was performed to assess transcriptomic changes in the myocardium.</div></div><div><h3>Results</h3><div>S/F-iTreg administration significantly improved left ventricular function and reduced myocardial fibrosis compared to those in controls. PKH26-labeled S/F-iTregs were detected within the cardiac tissue, confirming in vivo migration. RNA sequencing revealed downregulation of inflammation- and fibrosis-related pathways, including tumor necrosis factor-alpha/nuclear factor kappa-light-chain-enhancer of activated B cell, platelet-derived growth factor, transforming growth factor-beta signaling, and modulation of macrophage-related transcriptional programs.</div></div><div><h3>Conclusions</h3><div>Systemic administration of S/F-iTregs attenuates cardiac fibrosis and preserves cardiac function in pressure overload–induced heart failure. These findings support S/F-iTreg–based immunomodulation as a potential approach to limit adverse fibrotic cardiac remodeling.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101079"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378372","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":"Intra-articular injections of platelet-rich plasma suppress cartilage degeneration in a mouse model of knee osteoarthritis","authors":"Yasumasa Momoi ,&nbsp;Yoshitomo Saita ,&nbsp;Ryosuke Nakajima ,&nbsp;Sayuri Uchino ,&nbsp;Hirofumi Nishio ,&nbsp;Shin Fukusato ,&nbsp;Takanori Wakayama ,&nbsp;Yohei Kobayashi ,&nbsp;Atsushi Furuhata ,&nbsp;Hiroshi Ikeda ,&nbsp;Kazuo Kaneko ,&nbsp;Muneaki Ishijima","doi":"10.1016/j.reth.2026.101072","DOIUrl":"10.1016/j.reth.2026.101072","url":null,"abstract":"<div><h3>Introduction</h3><div>Pain-relieving drugs, such as nonsteroidal anti-inflammatory drugs and hyaluronic acid, are standard treatments for knee osteoarthritis (OA); however, no disease-modifying drugs exist for knee OA. Platelet-rich plasma (PRP) is a novel treatment with both symptom improvement and disease-modifying effects; however, the underlying mechanism remains unknown. In addition, the biologically active substances contained in PRP differ greatly depending on the purification method used. This controlled laboratory study aimed to investigate the therapeutic effects of two types of PRP with different white blood cell concentrations on knee OA using an animal model.</div></div><div><h3>Methods</h3><div>Leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) were prepared from 10-week-old female C57BL/6 mice. A mouse model of knee osteoarthritis was generated by the unilateral transection of the medial meniscus in the right hind limb. Mice were randomly assigned to three treatment groups that received 6 μL intra-articular injections of either phosphate-buffered saline (control), LR-PRP, or LP-PRP at 2-, 4-, and 6-weeks post-surgery. Mice were sacrificed 12 weeks post-surgery and histologic analysis, immunohistochemistry analysis for CD68 and three‐dimensional micro-computed tomography (3DμCT) of knee joints were analyzed. Hind limb weight-bearing distribution was measured preoperatively and at 4- and 12-weeks post-surgery. Statistical analyses were performed using GraphPad Prism 9.0.2. P-values of &lt;5 % were considered statistically significant.</div></div><div><h3>Results</h3><div>Histological analysis of the femoral medial condyle (Osteoarthritis Research Society International (OARSI) score) showed that both the LP and LR groups had significantly suppressed cartilage destruction compared with the Phosphate Buffered Saline (PBS) group (P = 0.01). The percentage of CD68-positive synovial macrophages in the lateral joint was significantly lower in the LR group than in the PBS group (PBS: 2.0 ± 2.9 %, LR: 0.6 ± 1.3 %, LP: 0.9 ± 1.9 %; P = 0.02). The affected-side load rate (%) increased in the LR and LP groups, with a significant increase observed in the LR group from week four. PBS group, Pre/4w/12w = 36.0 ± 4.8/33.8 ± 6.8/36.2 ± 7.4 % (P = 0.60); LR group, Pre/4w/12w = 31.9 ± 2.2/34.3 ± 8.3/44.2 ± 4.8 % (P &lt; 0.01); LP group, Pre/4w/12w = 33.5 ± 7.4/36.1 ± 7.4/42.0 ± 5.2 % (P = 0.02). Conversely, no significant difference in BMD was observed between groups.</div></div><div><h3>Conclusions</h3><div>Intra-articular injection of LR- and LP-PRP attenuated cartilage degeneration in the medial femoral condyle in a mouse model of knee osteoarthritis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101072"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077152","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}