Regenerative Therapy最新文献

{"title":"Targeting p53-p21 signaling to enhance mesenchymal stem cell regenerative potential","authors":"Ahsas Goyal ,&nbsp;Muhammad Afzal ,&nbsp;Nawaid Hussain Khan ,&nbsp;Kavita Goyal ,&nbsp;Suresh Kumar Srinivasamurthy ,&nbsp;Gaurav Gupta ,&nbsp;K. Benod Kumar ,&nbsp;Haider Ali ,&nbsp;Mohit Rana ,&nbsp;Ling Shing Wong ,&nbsp;Vinoth Kumarasamy ,&nbsp;Vetriselvan Subramaniyan","doi":"10.1016/j.reth.2025.03.007","DOIUrl":"10.1016/j.reth.2025.03.007","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are properties of self-renewal and differentiation potentials and thus are very appealing to regenerative medicine. Nevertheless, their therapeutic potential is frequently constrained by senescence, limited proliferation, and stress-induced apoptosis. The key role of the p53–p21 biology in MSC biology resides in safeguarding genomic stability while promoting senescence and limiting regenerative capacity upon over-activation demonstrated. This pathway is a key point for improving MSC function and exploiting the inherent limitations. Recent advances indicate that senescence can be delayed by targeting the p53-p21 signaling and improved MSC proliferation and differentiation capacity. PFT-α pharmacological agents transiently inhibit p53 from increasing proliferation and lineage-specific differentiation, while antioxidants such as hydrogen-rich saline and epigallocatechin 3 gallate (EGCG) suppress oxidative stress and attenuate p53 p21 signaling. Genetic tools like CRISPR-Cas9 and RNA interference also precisely modulate TP53 and CDKN1A expression to optimize MSC functionality. The interplay of p53-p21 with pathways like Wnt/β-catenin and MAPK further highlights opportunities for combinatorial therapies to enhance MSC resilience and regenerative outcomes. This review aims to offer a holistic view of how p53–p21 targeting can further the regenerative potential of MSCs, resolving senescence, proliferation, and stress resilience towards advanced therapeutics built on MSCs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 352-363"},"PeriodicalIF":3.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent progress in the identification and in vitro culture of skin organoids","authors":"Yanan Huang ,&nbsp;Qing Ye ,&nbsp;Jiyuan Wang ,&nbsp;Kaimin Zhu ,&nbsp;Haojie Yang ,&nbsp;Xiaoping Jiang ,&nbsp;Meihua Shen","doi":"10.1016/j.reth.2025.01.001","DOIUrl":"10.1016/j.reth.2025.01.001","url":null,"abstract":"<div><div>An organoid is a cell-based structure that shows organ-specific properties and shares a similar spatial organization as the corresponding organ. Organoids possess powerful capability to reproduce the key functions of the associated organ structures, and their similarity to the organs makes them physiologically relevant systems. The primary challenge associated with the development of skin organoids is the complexity of the human skin architecture, which encompasses the epidermis and the dermis as well as accessory structures, including hair follicles, sweat glands, and sebaceous glands, that perform various functions such as thermoregulation. The ultimate objectives of developing skin organoids are to regenerate the complete skin structure in vitro and reconstruct the skin in vivo. Consequently, safety, reliability, and the fidelity of the tissue interfaces are key considerations in this process. For this purpose, the present article reviews the most recent advances in this field, focusing on the cell sources, culture methods, culture conditions, and biomarkers for identifying the structure and function of skin organoids developed in vitro or in vivo. The subsequent sections summarize the recent applications of skin organoids in related disease diagnosis and treatments, and discuss the future prospects of these organoids in terms of clinical applications. This review of skin organoids can provide an important foundation for studies on human skin development, disease modeling, and reconstructive surgery, with broad utility for promising future opportunities in both biomedical research and clinical practice.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 341-351"},"PeriodicalIF":3.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel therapeutic strategies for Asherman's syndrome: Endometrial regeneration using menstrual blood-derived stem cells","authors":"Sena Awano-Kim,&nbsp;Satoshi Hosoya,&nbsp;Ryo Yokomizo,&nbsp;Hiroshi Kishi,&nbsp;Aikou Okamoto","doi":"10.1016/j.reth.2025.03.019","DOIUrl":"10.1016/j.reth.2025.03.019","url":null,"abstract":"<div><div>Endometrium is vital to the establishment of pregnancy through its cyclical regeneration, which, when disrupted, can lead to endometrial thinning and Asherman's syndrome (AS). AS is characterized by infertility, pelvic pain, menstrual irregularities, and placental complications. Currently, treatments such as hysteroscopic adhesiolysis and hormone replacement therapy have demonstrated variable efficacy with limited clinical evidence. Recent developments in cell therapy have introduced menstrual blood-derived mesenchymal stem cells (MenSCs) as a promising alternative therapeutic strategy. Menstrual blood offers a noninvasive, periodically available source of mesenchymal stem cells, MenSCs for endometrial regeneration. This review comprehensively examines the endometrial regenerative process, pathophysiology of AS, and therapeutic prospects of MenSCs, underscoring the need for continued research to optimize treatment strategies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 328-340"},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-culture with adipose mesenchymal stem cells promotes Blastocyst formation and gene expression in embryos from aged mice","authors":"Yan-Der Hsuuw ,&nbsp;Yu-Ting Su ,&nbsp;Wen-Hsiung Chan ,&nbsp;Cheng-Chun Wu ,&nbsp;Yu-Chieh Tsai ,&nbsp;Hou-Chun Chen ,&nbsp;Fu-Jen Huang ,&nbsp;Chuen-Fu Lin","doi":"10.1016/j.reth.2025.03.017","DOIUrl":"10.1016/j.reth.2025.03.017","url":null,"abstract":"<div><div>Recent studies have highlighted the positive effects of co-culturing embryos with stem cells on embryo development in various mammalian systems. Stem cells secrete numerous factors, including cytokines, growth factors, and microRNAs, which promote embryo development. However, the impact of stem cells on the development of embryos derived from aged mice's oocytes remains poorly understood. This study evaluated the co-culture effects of adipose tissue-derived mesenchymal stem cells (ADMSCs) on zygotes, focusing on the developmental potential of fertilized embryos. Embryo quality was assessed through staining techniques to measure trophectoderm (TE), inner cell mass (ICM), and total blastocyst cell numbers during <em>in vitro</em> culture. Results demonstrated that ADMSC co-culture significantly improved zygote cleavage and blastocyst development rates, particularly in embryos derived from aged mice. Enhanced implantation and post-implantation potential were observed in embryos from both young and aged mice. Notably, co-culture increased TE, ICM, and total blastocyst cell numbers in aged mice-derived embryos without inducing apoptosis in blastocysts. Gene expression analysis revealed upregulation of <em>OCT4 and G6PDH,</em> associated with pluripotency and glucose metabolism, particularly in embryos from aged mice, while the heat stress marker HSP70 showed no significant changes. These findings demonstrate the potential of ADMSC co-culture as a beneficial protocol for improving embryo development. These findings from this study could offer an important basis for future mechanistic studies in this area.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 319-327"},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-derived extracellular vesicles: Precision miRNA delivery for overcoming cancer therapy resistance","authors":"Ahsas Goyal ,&nbsp;Muhammad Afzal ,&nbsp;Kavita Goyal ,&nbsp;Subbulakshmi Ganesan ,&nbsp;Mukesh Kumari ,&nbsp;S. Sunitha ,&nbsp;Aniruddh Dash ,&nbsp;Suman Saini ,&nbsp;Mohit Rana ,&nbsp;Gaurav Gupta ,&nbsp;Haider Ali ,&nbsp;Ling Shing Wong ,&nbsp;Vinoth Kumarasamy ,&nbsp;Vetriselvan Subramaniyan","doi":"10.1016/j.reth.2025.03.006","DOIUrl":"10.1016/j.reth.2025.03.006","url":null,"abstract":"<div><div>Cancer remains a prominent worldwide health concern, presenting existing therapies with frequent difficulties, including major toxicity, limited effectiveness, and treatment resistance emergence. These issues highlight the necessity for novel and enhanced remedies. Exosomes, tiny extracellular vesicles that facilitate intercellular communication, have attracted interest for their potential medicinal applications. Carrying a variety of molecules, including microRNAs, small interfering RNAs, long non-coding RNAs, proteins, lipids, and DNA, these vesicles are positioned as promising cancer treatment options. Current studies have increasingly investigated the capacity of microRNAs as a strategic approach for combating malignancy. Mesenchymal stem cells (MSC) are recognized for their aptitude to augment blood vessel formation, safeguard against cellular death, and modulate immune responses. Consequently, researchers examine exosomes derived from MSCs as a safer, non-cellular choice over therapies employing MSCs, which risk undesirable differentiation. The focus is shifting towards employing miRNA-encapsulated exosomes sourced from MSCs to target and heal cancerous cells selectively. However, the exact functions of miRNAs within MSC-derived exosomes in the context of cancer are still not fully understood. Additional exploration is necessary to clarify the role of these miRNAs in malignancy progression and to pinpoint viable therapeutic targets. This review offers a comprehensive examination of exosomes derived from mesenchymal stem cells, focusing on the encapsulation of miRNAs, methods for enhancing cellular uptake and stability, and their potential applications in cancer treatment. It also addresses the difficulties linked to this methodology and considers future avenues, including insights from current clinical oncology research.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 303-318"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of gelatine/fucoidan nanogel-coated silver nanoparticles for the treatment of wound healing therapy and nursing care","authors":"Jiao Hao ,&nbsp;Xiaozhen Liu ,&nbsp;Yaomiao Du","doi":"10.1016/j.reth.2025.03.001","DOIUrl":"10.1016/j.reth.2025.03.001","url":null,"abstract":"<div><div>Microbial infections and tissue damage by dressing removal are common problems in wound healing. In this study, gelatine/fucoidan nanogel coated with silver nanoparticles (Ag@Gel/Fu) by simple polymerization technique to assess the antibacterial potential Against human infectious pathogens and wound healing activity Against L929 fibroblast cells. The incorporation of silver nanoparticles in Ag@Gel/Fu nanogel was confirmed by UV–vis, XRD, and SEM analysis techniques. The results of the antibacterial assay revealed that the Ag@Gel/Fu nanogel showed excellent bacterial growth reduction and zone of inhibition against <em>Escherichia coli</em> and <em>Staphylococcus aureus,</em> depending upon the concentrations. In vitro wound healing results exhibit rapid regeneration of L929 cells in a short duration. It has more advantages, such as Ag@Gel/Fu, to prevent damage to outer skin tissue by infections. It is the more significant bacterial and biofilm infection control of the wound sites. The overall results confirmed that coating of biopolymer and marine polysaccharide fucoidan enhances the biological property of Ag@Gel/Fu nanogel and wound healing potential. Ag@Gel/Fu nanogel co-culture with fibroblast cells showed no cytotoxic effect after 48 h. Finally, Ag@Gel/Fu nanogel is an effective material for infected wound healing nursing care applications.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 282-291"},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo evaluation of biocompatibility and biodegradation of porcine collagen membranes","authors":"Seon Ae Kim ,&nbsp;Eun Jeong Go ,&nbsp;Bo Seung Bae ,&nbsp;Jae Woong Jung ,&nbsp;Mi-La Cho ,&nbsp;Asode Ananthram Shetty ,&nbsp;Seok Jung Kim","doi":"10.1016/j.reth.2025.03.015","DOIUrl":"10.1016/j.reth.2025.03.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Collagen-based materials differ in absorption time, biodegradation patterns, and inflammatory cell infiltration. This study aimed to evaluate the biocompatibility and biodegradation of native, differently processed, and cross-linked porcine collagen membranes implanted in the subcutaneous tissue of rats, following ISO 10993-6:2016.</div></div><div><h3>Methods</h3><div>Sixty Sprague–Dawley rats were randomly divided into four groups: Group 1 (lyophilized 3 % porcine type I collagen membrane), Group 2 (lyophilized 3 % porcine type I collagen membrane, dehydrothermal [DHT]), Group 3 (1,4-butanediol diglycidyl ether [BDDE] cross-linked, lyophilized 3 % porcine type I collagen), and Group 4 (BDDE cross-linked, lyophilized 3 % porcine type I collagen, DHT). The experimental periods were 1, 2, 4, 8, and 12 weeks, with three animals per group per period. After each period, specimens were extracted and analyzed for membrane structure, biodegradation, cell infiltration, angiogenesis, tissue integration, and foreign body reaction using histological staining and scoring according to ISO 10993-6:2016.</div></div><div><h3>Results</h3><div>The cross-linked collagen membrane groups maintained their porous structure, with cell infiltration and blood vessel formation observed within this structure. Non-cross-linked collagen membranes (Group 1) appeared as lumps under the subcutaneous tissue and exhibited minimal or no response throughout the observation periods. Groups 2 and 4 biodegraded the fastest. Group 2 membranes were not detected in the subcutaneous tissue at 8 weeks, classified as a slight response. Cross-linked collagen membranes in all groups showed a slight response, whereas Group 4 exhibited a moderate response (11.0–16.9) only at 12 weeks. The tissue response to collagen membranes in all groups aligned with physiological inflammatory processes, scoring from minimal or no response (0.0–5.9) to slight response (6.0–10.9), confirming their biocompatibility.</div></div><div><h3>Conclusions</h3><div>Cross-linking methods, temperature, and chemical reagents influence collagen membrane properties. Cross-linked collagen formed a porous structure, and high-temperature DHT cross-linking accelerated the biodegradation of the collagen membrane.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 292-302"},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel breast reconstruction technique using ex vivo mononuclear (RE-01) cells and adipose-derived mesenchymal stem cells","authors":"Ayana Shikanai ,&nbsp;Satomi Furukawa ,&nbsp;Sen Jiang ,&nbsp;Satoshi Fujimura ,&nbsp;Goro Kutomi ,&nbsp;Mitsue Saito ,&nbsp;Rica Tanaka","doi":"10.1016/j.reth.2025.03.018","DOIUrl":"10.1016/j.reth.2025.03.018","url":null,"abstract":"<div><h3>Introduction</h3><div>Breast reconstruction using fat grafts presents challenges; for example, fat necrosis owing to inadequate blood flow results in reduced engraftment rates. Supplementation of adipose tissue with adipose-derived mesenchymal stem cells (ADSCs) to promote the rapid vascularization of transplanted tissue has been investigated. However, the vascularization of fat-grafted tissues using only ADSC transplantation is limited. <em>Ex vivo</em> cultured mononuclear cells (RE-01) are a cell population with highly vascular and tissue-regenerative properties. This study aimed to evaluate the effect of combining RE-01 cells and ADSCs on the engraftment rate of fat grafts and explore the potential of this approach as a new option for breast reconstruction surgery. We hypothesized that combining RE-01 with ADSCs might promote angiogenesis and improve the fat grafting rate, consequently reducing the number of ADSCs required.</div></div><div><h3>Methods</h3><div>ADSCs cultured from human adipose tissue discarded during liposuction were co-cultured with RE-01 cells produced from the peripheral blood of healthy volunteers. <em>In vitro</em> vascular regeneration and adipogenic differentiation potential were analyzed. In addition, fat grafting experiments were conducted using nude mice to verify the fat grafting efficacy of ADSCs after co-cultivation with RE-01.</div></div><div><h3>Results</h3><div>ADSCs co-cultured with RE-01 cells promoted angiogenesis and adipogenesis <em>in vitro</em>. This was evidenced by a significant increase in the expression of adipogenic markers <em>FABP4</em> and <em>PPARγ</em>, as well as enhanced lipid droplet formation observed through Oil Red O staining. The <em>in vivo</em> results demonstrated that the fat engraftment rate was significantly improved in the mixed group of ADSCs co-cultured with RE-01 cells. The number of blood vessels and fat quality of the transplanted adipose tissue were also increased in this group, suggesting that ADSCs co-cultured with RE-01 cells were highly effective in fat transplantation.</div></div><div><h3>Conclusions</h3><div>ADSCs co-cultured with RE-01 cells may be useful for improving the engraftment rate of fat grafts. However, further studies are required to verify the mechanisms.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 271-281"},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic vesicles inhibit bone marrow adiposity via wnt/β-catenin signaling","authors":"Yuan Zhu ,&nbsp;Yaoshan Liu ,&nbsp;Kunkun Yang ,&nbsp;Weiliang Wu ,&nbsp;Yawen Cheng ,&nbsp;Yanan Ding ,&nbsp;Ranli Gu ,&nbsp;Hao Liu ,&nbsp;Xiao Zhang ,&nbsp;Yunsong Liu","doi":"10.1016/j.reth.2025.03.012","DOIUrl":"10.1016/j.reth.2025.03.012","url":null,"abstract":"<div><h3>Background</h3><div>There is currently increasing focus on aging-related diseases. Osteoporosis is a common disease the incidence of which increases with age. In older patients with osteoporosis, bone marrow mesenchymal stem cells (BMMSCs) have a decreased capacity for osteogenesis and an increased capacity for adipogenesis, causing excessive accumulation of adipose tissue in the bone marrow. Therefore, means of reducing bone marrow adiposity may have therapeutic potential for osteoporosis. Apoptotic vesicles (apoVs) participate in a wide range of physiological processes and have been shown to have therapeutic effects in a variety of diseases. The principal objective of this study was to examine the special properties and regulatory mechanisms of BMMSC-derived apoVs in the treatment of bone marrow adiposity.</div></div><div><h3>Results</h3><div>The results showed that apoVs could decrease bone marrow adiposity in osteoporotic mice and prevent adipogenic differentiation of MSCs by activating the Wnt/β-catenin pathway.</div></div><div><h3>Conclusion</h3><div>New apoV-based therapies have potential for the treatment of bone marrow adiposity in patients with aging-related osteoporosis and may be further applicable to the treatment of obesity and aging-related diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 262-270"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal frequency of platelet-rich plasma injections for managing osteoarthritis: A longitudinal study","authors":"Masahiko Kemmochi","doi":"10.1016/j.reth.2025.02.006","DOIUrl":"10.1016/j.reth.2025.02.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent reviews suggest that PRP injections can improve pain and function more effectively than other treatments; however, consensus on the optimal number of injections is lacking. We aimed to determine the optimal administration frequency and number of PRP injections for management of osteoarthritis (OA) symptoms, to examine long-term effects and structural improvements with PRP, and to determine correlations between clinical outcomes and imaging findings.</div></div><div><h3>Methods</h3><div>This longitudinal study included 167 patients with knee OA, categorized using the Kellgren–Lawrence (KL) grading system. Participants received up to six PRP injections and were followed-up for 24 months. Pain levels were assessed using the visual analog scale (VAS); functional recovery was measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS). To determine whether PRP can induce sustained structural improvements, we used the MRI Osteoarthritis Knee Score (MOAKS) to monitor changes in bone-marrow lesions (BMLs). Data were analyzed using repeated-measures analysis of variance to identify significant changes in pain and functional outcomes.</div></div><div><h3>Results</h3><div>VAS and KOOS scores significantly improved after PRP treatment. Patients with KL grades 1 and 2 exhibited maximum pain relief after the fourth injection; those with KL grades 3 and 4 showed optimal results after the fifth injection. Improvements were maintained or enhanced at the 24-month follow-up. The effect size increased as the number of treatments progressed, and especially after the fourth treatment, with a Cohen's d values of −1.22, −1.28, and −0.99 (p &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>PRP injections administered at specific intervals can significantly reduce pain and improve function in patients with OA, with the required frequency depending on disease severity. These findings support the customization of PRP-treatment protocols based on individual patient profiles to maximize therapeutic benefits.</div></div><div><h3>Trial registration</h3><div>This study has been registered with the clinical trial register of the Japan Medical Association Center for Clinical Trials (JMA-IIA00351).</div></div><div><h3>Unblinded study registration</h3><div>This study has been registered with the clinical trial register of the Japan Medical Association Center for Clinical Trials (JMA-IIA00351).</div></div><div><h3>Level of evidence</h3><div>II.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"29 ","pages":"Pages 227-236"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}