Regenerative Therapy最新文献

{"title":"Influence of donor–recipient age differences in allogenic rat thyroid transplantation","authors":"Ayumi Arauchi ,&nbsp;Katsuhisa Matsuura ,&nbsp;Tatsuya Shimizu","doi":"10.1016/j.reth.2025.101047","DOIUrl":"10.1016/j.reth.2025.101047","url":null,"abstract":"<div><h3>Introduction</h3><div>Regenerative medicine for tissue dysplasia, hypoplasia, and functional impairment of tissues and cells has advanced considerably, and thyroid disease is no exception. Inducing differentiation of thyroid cells from patient-derived cells and transplanting them back into patients is an ideal approach because it eliminates the need for immunosuppressive drugs. However, the relationship between the maturity of cells or tissues derived from various sources and engraftment outcomes remains unclear. In this study, we evaluated the effect of donor–recipient age differences using thyroids from living rat donors, given the current lack of sufficiently mature stem cell-derived thyroid tissue.</div></div><div><h3>Methods</h3><div>Histological and gene expression differences were analyzed in thyroids of retired rats (&gt;20 weeks old with impaired reproductive function) and 3-week-old rats. Thyroid transplantation experiments were conducted between age-matched or age-mismatched groups. Donor thyroids were implanted beneath the renal capsule of recipient rats without total thyroidectomy, and grafts from retired rats transplanted into 3-week-old rats were resected 1 and 6 months post-transplantation, while others were resected 1 month post-transplantation for immunohistological analysis and gene expression analysis of thyroid differentiation markers.</div></div><div><h3>Results</h3><div>Thyroids from 3-week-old rats and retired rats showed minimal histological and functional differences; however, the expression levels of several thyroid-specific marker genes were significantly higher in retired rats. When thyroids were transplanted between age-matched donors and recipients, clear engraftment was observed at 1 month. Although robust engraftment was also observed when thyroids from retired rats were transplanted into 3-week-old recipients at both 1 and 6 months, transplantation of thyroids from 3-week-old donors into retired rats resulted in disrupted follicular structures and fibrotic changes at 1 month. In contrast, mRNA expression levels of transplanted thyroids presented no significant differences between age-matched and age-mismatched transplantation.</div></div><div><h3>Conclusions</h3><div>Mismatch between donor thyroid maturity and recipient age may influence engraftment in rat allogenic thyroid transplantation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101047"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691074","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":"Butyrate-preconditioned human adipose-derived stem cell-conditioned medium enhances myocardial perfusion after infarction","authors":"Shinji Kobuchi ,&nbsp;Wan-Tseng Hsu ,&nbsp;Misaki Matsuzawa ,&nbsp;Rina Kagawa ,&nbsp;Junko Watanabe ,&nbsp;Koki Harada ,&nbsp;Yuki Toda ,&nbsp;Shohei Hamada ,&nbsp;Masayuki Tsujimoto ,&nbsp;Hidekazu Kawashima ,&nbsp;Kaneyasu Nishimura ,&nbsp;Kenjiro Matsumoto ,&nbsp;Kazuyuki Takata","doi":"10.1016/j.reth.2025.11.007","DOIUrl":"10.1016/j.reth.2025.11.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Adipose-derived stem cell-conditioned medium (ASC-CM) is promising for cardiac repair via paracrine mechanisms. However, variability in efficacy limits its clinical translation. We investigated whether preconditioning human ASC with butyrate (ASC-BA-CM) enhanced its paracrine potency and improved <em>in vitro</em> and <em>in vivo</em> outcomes.</div></div><div><h3>Method</h3><div>RNA-sequencing of human ASCs treated with butyrate was performed to characterize transcriptomic changes. CM was collected and analyzed via cytokine/chemokine arrays. Wound healing assays using human umbilical vein endothelial cells (HUVECs), with and without THP-1 macrophage co-culture, were performed to evaluate endothelial repair and its correlations with secreted factors. <em>In vivo</em> angiogenesis was assessed using a sponge implantation model, and myocardial perfusion was measured in a rat myocardial infarction model using single-photon emission computed tomography/computed tomography (SPECT/CT) thallium-201 imaging.</div></div><div><h3>Results</h3><div>Butyrate preconditioning upregulated angiogenesis- and immune-related genes, including <em>CXCL8</em>, <em>SOD2</em>, and <em>TGM2</em>. It increased IL-10, CXCL5, and MMP-1 secretion. <em>In vitro</em>, BA-preconditioned ASC-CM enhanced HUVEC wound closure, which was improved by co-culture with THP-1 macrophages and negatively correlated with TGFb3 and TIMP-2 levels. <em>In vivo</em>, ASC-BA-CM promoted vascularization and macrophage accumulation in sponges and significantly improved myocardial perfusion by approximately 32 % compared with controls.</div></div><div><h3>Conclusions</h3><div>Butyrate preconditioning enhanced the paracrine activity of ASC-CM and was associated with improved myocardial perfusion in a rat model. These findings suggest that butyrate may augment the ASC secretome function. Potential mechanisms such as endothelial repair, angiogenesis, and immune modulation remain hypothetical and require further validation in future studies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101042"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578352","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 a digital analysis system for a novel 3D culture-based colony formation to detect malignantly transformed cells in human cell-based therapeutic products","authors":"Shinji Kusakawa ,&nbsp;Tingshu Yang ,&nbsp;Rumi Sawada ,&nbsp;Ryuji Kato ,&nbsp;Yoji Sato ,&nbsp;Satoshi Yasuda","doi":"10.1016/j.reth.2025.101052","DOIUrl":"10.1016/j.reth.2025.101052","url":null,"abstract":"<div><h3>Introduction</h3><div>The presence of malignantly transformed cells in human cell-based therapeutic products (hCTPs) is a significant safety concern. Although such cellular impurities in hCTPs can be assessed by detecting anchorage-independent growth using conventional soft agar colony formation (SACF) assays, the sensitivity of these assays is often insufficient. To overcome this limitation, we previously developed a novel tumorigenicity-associated testing method, the digital SACF (D-SACF) assay, which combines a partitioned culture of test cells to concentrate target cells with colony detection via image analysis. However, conventional soft agar culture involves complicated operations, such as preparing multilayered agar media and temperature control, and further technical optimization is required for the widespread adoption of the D-SACF assay.</div></div><div><h3>Methods</h3><div>In this study, we focused on a new culture system incorporating a three-dimensional (3D) culture method using a liquid medium containing the low-molecular-weight agar polymer LA717 in low-adhesion culture vessels. We initially confirmed conditions for the efficient high-density 3D culture of normal cells using LA717-supplemented medium in low-adhesion 96-well plates.</div></div><div><h3>Results</h3><div>Using human mesenchymal stem/stromal cells (MSCs) as a normal cell model and HeLa cells as a transformed cell model, we demonstrated that the new 3D culture system effectively maintained the dispersion of MSCs and prevented their aggregation, while transformed HeLa cells exhibited robust anchorage independence, thereby establishing the new liquid/low-molecular-weight agar colony formation (LACF) method as an alternative to SACF.</div></div><div><h3>Conclusions</h3><div>Finally, by systematizing the digital analysis system for the LACF assay (D-LACF assay), which streamlines the overall workflow from the performance evaluation of the test method to product testing and result interpretation, the limitations of the conventional soft agar-based D-SACF assay were addressed, and its practicality and utility were enhanced. This <em>in vitro</em> evaluation system is expected to provide a promising approach for improving the quality and safety of hCTPs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101052"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796775","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":"Monthly multiple injections of leukocyte-poor platelet-rich plasma (ACP®) for knee osteoarthritis: clinical effectiveness across KL grades, dose-response plateau at four, and 24-month durability","authors":"Masahiko Kemmochi","doi":"10.1016/j.reth.2026.101067","DOIUrl":"10.1016/j.reth.2026.101067","url":null,"abstract":"<div><h3>Background</h3><div>Monthly, ultrasound-guided intra-articular injections of leukocyte-poor platelet-rich plasma (ACP®) are widely used for knee osteoarthritis (KOA), but optimal dosing and cumulative exposure remain unclear.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed prospectively planned ACP treatments at a single clinic. Knees with KL1-4 received fixed per-knee doses (3 mL [3A] or 6 mL [6A]) monthly up to six sessions. Primary outcome was VAS pain; secondary outcomes were KOOS (Pain/ADL/QoL), OMERACT-OARSI response, MOAKS-BML, and joint effusion (JF). ANCOVA for ΔVAS at 12 months adjusted for baseline VAS and prespecified covariates; longitudinal mixed-effects models and segmented regression assessed dose-response and breakpoint.</div></div><div><h3>Results</h3><div>Pain improved at 12 months (n = 115) and was maintained at 24 months (n = 67). Segmented regression identified a dose-response plateau around the 4th injection. The 6 mL regimen showed no robust adjusted advantage over 3 mL at 12 months. KOOS domains and OMERACT-OARSI responder rates improved at 12 months and persisted at 24 months. MOAKS-BML decreased from 12 to 24 months; JF tended to decline. No serious adverse events related to ACP injections were documented.</div></div><div><h3>Conclusions</h3><div>Under a fixed monthly protocol mirroring our LR-PRP schedule, ACP (LP-PRP) produced clinically meaningful improvements across KL1-4 with a practical evaluation horizon through the 4th injection and no clear per-session volume benefit of 6 mL over 3 mL. Prospective randomization of dose within a monthly-multiple framework is warranted.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101067"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037165","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":"Recent progress in immunomodulation-based strategies for bone repair","authors":"Wang Yuqiang,&nbsp;Zhang Ziyan,&nbsp;Sun Xuedi,&nbsp;Piao Chengdong","doi":"10.1016/j.reth.2025.101054","DOIUrl":"10.1016/j.reth.2025.101054","url":null,"abstract":"<div><div>Bone regeneration is a highly coordinated process shaped by the interplay between immune responses and osteogenic mechanisms. Immune cells such as neutrophils, macrophages, T cells, and B cells dynamically regulate the local microenvironment through cytokine secretion and signaling pathways, thereby influencing osteogenesis, angiogenesis and bone remodeling, while dysregulated or prolonged inflammation can disrupt healing. Growing evidence has highlighted the potential of leveraging immunomodulation to enhance bone repair. This review synthesizes recent progress in immunoregulatory strategies by comparing cellular therapies, molecular interventions and biomaterial-based approaches in terms of their mechanisms, their effects on osteogenesis and angiogenesis, and their translational potential. Particular emphasis is placed on immune cell specific signaling pathways, biomaterial design parameters including surface topography, porosity, ion release and stiffness, and emerging technologies such as immune responsive hydrogels, programmable scaffolds and exosome based delivery systems. Current findings indicate that mesenchymal stem cells and regulatory T cells not only provide progenitor sources but also reshape the immune milieu through paracrine factors and exosomes; cytokines, small molecules, microRNAs and pro resolving mediators effectively modulate inflammatory cascades to promote vascularized bone formation; and immunomodulatory biomaterials enable spatiotemporal regulation of macrophage polarization, particularly the transition from the pro inflammatory M1 phenotype to the reparative M2 phenotype. Collectively, these advances highlight that bone repair is fundamentally an immunologically driven process, and integrating temporal immune regulation with emerging therapeutic platforms offers a promising pathway toward precise and personalized bone regeneration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101054"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839205","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":"Tissue and organ engineering: Investor sentiments and analysis","authors":"Frida Velcani ,&nbsp;Erica Keyes ,&nbsp;José Luis Caraveo III ,&nbsp;James Reohr ,&nbsp;Craig D'Cruz ,&nbsp;Andrew Osterman ,&nbsp;Deirdre C. O'Donnell","doi":"10.1016/j.reth.2026.101066","DOIUrl":"10.1016/j.reth.2026.101066","url":null,"abstract":"<div><h3>Introduction</h3><div>Regenerative medicine involves restoring natural function by replacing or regenerating human cells, tissues, or organs. Despite projections of significant market growth, venture capital (VC) investment in tissue and organ engineering has recently declined.</div></div><div><h3>Methods</h3><div>We conducted a mixed-methods study using structured surveys and qualitative interviews. VC investors with experience in healthcare sectors (biotechnology, tissue engineering, and medical technology) were invited to complete a survey and participate in interviews.</div></div><div><h3>Results</h3><div>We received 22 survey responses and conducted 9 interviews (April–May 2025). Prior exposure to regenerative medicine was significantly associated with future investment likelihood (p = 0.0464). Investment potential strongly correlated with assets under management (ρ = 0.67) and investment stage (ρ = 0.66). Among 20 respondents, clinical validation (n = 8) and adoption (n = 8) were most often cited as major investment drivers, followed by reimbursement and regulatory challenges. Interviews emphasized four factors shaping VC interest in tissue and organ engineering: prior investment experience, time horizon misalignment, clinical risk expectations, and market readiness.</div></div><div><h3>Discussion</h3><div>Startups can improve appeal by targeting long-horizon investors, outlining clinical and regulatory pathways, and generating robust, comparative evidence to support value-based reimbursement.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101066"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976705","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 stromal cell administration promotes macrophage-mediated bile duct regeneration","authors":"Takanori Igarashi ,&nbsp;Naruhiro Kimura ,&nbsp;Hiroyuki Abe ,&nbsp;Tomoaki Yoshida ,&nbsp;Yusuke Watanabe ,&nbsp;Hiroteru Kamimura ,&nbsp;Akira Sakamaki ,&nbsp;Takeshi Yokoo ,&nbsp;Kenya Kamimura ,&nbsp;Atsunori Tsuchiya ,&nbsp;Shuji Terai","doi":"10.1016/j.reth.2026.101065","DOIUrl":"10.1016/j.reth.2026.101065","url":null,"abstract":"<div><h3>Introduction</h3><div>Mesenchymal stromal cell (MSC) therapy is used in cirrhosis models of chronic hepatocellular damage and represents a novel therapeutic approach for liver regeneration. However, no studies have examined MSC therapy for bile duct injury and its effects on bile duct regeneration. This study aimed to elucidate the mechanism underlying bile duct regeneration by establishing a regeneration model and administering MSCs.</div></div><div><h3>Methods</h3><div>A model of bile duct regeneration was developed by feeding mice a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet to induce bile duct injury, followed by a normal diet to promote bile duct regeneration. MSCs were administered concurrently with the normal diet, and the livers were analyzed after 2 days. An experimental system was also developed in which clodronate liposomes were administered alongside MSCs to eliminate the influence of macrophages.</div></div><div><h3>Results</h3><div>MSC administration significantly increased the rate of body weight gain and the liver-to-body weight ratio on day 2 after the change to a normal diet. Immunostaining revealed an increase in the number of CK19⁺ cholangiocytes. The numbers of Hnf4α⁺ and Sox9⁺ cells were significantly elevated in the MSC-treated group. Flow cytometric analysis of liver lymphocytes showed a significant increase in the number of Ly6C⁻ macrophages in the MSC-treated group. Furthermore, analysis of liver lymphocyte populations and cap analysis of gene expression revealed alterations in the immune response and macrophage-related genes, whereas macrophage removal during MSC treatment abolished the bile duct regenerative effects observed with MSC treatment.</div></div><div><h3>Conclusions</h3><div>Macrophages play a crucial role in bile duct regeneration, and MSC administration has regenerative effects. This approach has potential as a novel treatment modality for bile duct injuries.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101065"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181860","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":"Hypoxia-preconditioned bone marrow mesenchymal stem cell-derived exosomes ameliorate knee osteoarthritis by promoting cartilage regeneration and alleviating pain in rats","authors":"Binbin Zhang,&nbsp;Chuan Lu,&nbsp;Bin Dou,&nbsp;Wenzuo Gu,&nbsp;Kewen Li","doi":"10.1016/j.reth.2025.101049","DOIUrl":"10.1016/j.reth.2025.101049","url":null,"abstract":"<div><h3>Objective</h3><div>Knee osteoarthritis (KOA) is the most prevalent subtype of arthritis, characterized by progressive degeneration of articular cartilage. The present study aimed to investigate the reparative potential of exosomes derived from hypoxia-preconditioned bone marrow mesenchymal stem cells (Hypo-BMSCs-Exos) in treating cartilage damage associated with KOA.</div></div><div><h3>Methods</h3><div>An in vitro KOA chondrocyte model was established through induction with interleukin-1β (IL-1β). Subsequently, the modeled chondrocytes were co-cultured with Hypo-BMSCs-Exos. Flow cytometry, Western blotting, immunofluorescence staining, and senescence-associated β-galactosidase (SA-β-gal) staining were used to evaluate the effects of Hypo-BMSCs-Exos on chondrocyte proliferation, apoptosis, extracellular matrix (ECM) metabolic homeostasis, and cellular senescence. For in vivo assessment of Hypo-BMSCs-Exos efficacy, exosomes were administered to KOA model rats via intra-articular injection. Histological scoring, Micro-CT, pain behavioral assessments, and immunohistochemical analysis were then performed to determine the reparative effects of Hypo-BMSCs-Exos on cartilage damage.</div></div><div><h3>Results</h3><div>Hypo-BMSCs-Exos exerted superior effects in suppressing inflammatory responses, apoptosis, ECM degradation, and cellular senescence in rat chondrocytes. Specifically, treatment with Hypo-BMSCs-Exos upregulated the expression of ECM synthesis-related proteins (Collagen II, aggrecan) while downregulating the expression of ECM degradation-related proteins (ADAMTS-5, MMP-13), pro-inflammatory cytokines (iNOS, COX2), and key senescence-associated proteins (p53, p21, p16). Additionally, a reduction in the number of SA-β-gal-positive senescent chondrocytes was observed. In vivo experiments revealed that intra-articular injection of Hypo-BMSCs-Exos in KOA rats significantly improved the inflammatory microenvironment within the joint, promoted articular cartilage regeneration, and restored the structural integrity of subchondral bone. Furthermore, in vivo findings demonstrated that Hypo-BMSCs-Exos significantly regulated the expression of pain-related molecules and exerted a marked inhibitory effect on pain-related behaviors in KOA rats.</div></div><div><h3>Conclusion</h3><div>Hypo-BMSCs-Exos can effectively alleviate cartilage degeneration and pain in KOA, thus offering a novel and promising cell-free therapeutic strategy for the intervention of KOA.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101049"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691073","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":"Harnessing stromal vascular fraction-based therapies for wound healing: Mechanisms, synergies, and clinical translation","authors":"Jing Wu ,&nbsp;Yao Wang ,&nbsp;Wenjie Chen ,&nbsp;Min Lin ,&nbsp;Jinwen Jiang ,&nbsp;Hongde Jiang ,&nbsp;Zehuan Li ,&nbsp;Kailei Xu ,&nbsp;Bin Zhang","doi":"10.1016/j.reth.2025.08.012","DOIUrl":"10.1016/j.reth.2025.08.012","url":null,"abstract":"<div><div>Wound healing remains a major challenge in contemporary medicine, particularly with the increasing incidence of chronic wounds, such as those associated with diabetes and thermal injuries. Current treatments such as vacuum sealing drainage, topical therapies, and autologous skin grafting are limited by issues like poor therapeutic efficacy, frequent dressing changes, and immune responses. Cell-based therapies have shown promise but are hindered by single-cell type limitations and hostile wound microenvironments. The stromal vascular fraction (SVF) has emerged as a potential solution, where the enzymatic digestion (E-SVF) contains various cell types, including adipose-derived stem cells (ADSCs), endothelial cells, and fibroblasts, while mechanical digestion (M-SVF) introduces additional extracellular matrix (ECM), termed stromal vascular matrix (SVM). This review systematically evaluates the applications of SVF and SVM in wound healing. SVF promotes wound repair through proangiogenic, immunomodulatory, and ECM remodeling effects. When combined with platelet-rich plasma (PRP) or biomaterials, its efficacy is further enhanced through the synergistic regulation of inflammation and angiogenesis. SVM, with preserved ECM, and SVM-conditioned medium (SVM-CM), rich in growth factors, demonstrate superior wound healing capabilities compared to conventional SVF. Despite the challenges posed by impaired viability and function of aged SVF-derived ADSCs and the low mechanical properties of SVM, emerging technologies, such as 3D cell cultures to enhance stemness and the integration of other biomaterials to improve mechanical strength, offer promising solutions. This review highlights the potential of SVF as an autologous, multifunctional strategy to address unmet needs in wound healing and provides insights into future clinical applications and research directions.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 692-709"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative potential of PRP-based scaffolds in chronic wound healing: Mechanisms, advances, and therapeutic insights","authors":"Farag M.A. Altalbawy ,&nbsp;Bilal Abdul Majeed Mukhlif ,&nbsp;Ahemad Hussen ,&nbsp;Jaafaru Sani Mohammed ,&nbsp;Renuka Jyothi S ,&nbsp;Arshdeep Singh ,&nbsp;Shakti Bedanta Mishra ,&nbsp;Ashish Singh Chauhan ,&nbsp;Mohammad Ebrahim Astaneh ,&nbsp;Narges Fereydouni","doi":"10.1016/j.reth.2025.06.008","DOIUrl":"10.1016/j.reth.2025.06.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers often remain trapped in the inflammatory phase due to oxidative stress, protease overactivity, and impaired cellular responses, particularly in diabetic conditions. These wounds require advanced therapeutic strategies beyond conventional care. Regenerative medicine—especially platelet-rich plasma (PRP)-based interventions—has emerged as a promising approach for enhancing wound repair.</div></div><div><h3>Methods</h3><div>This review examines recent developments in PRP-loaded scaffolds, focusing on their biological mechanisms, structural advantages, and clinical applications. It synthesizes findings from key studies that integrate PRP with natural and synthetic biomaterials, often combined with bioactive agents like adipose-derived stem cell exosomes.</div></div><div><h3>Results</h3><div>PRP-containing scaffolds promote wound healing through multiple pathways: enhancing cell proliferation, migration, angiogenesis, and extracellular matrix remodeling; reducing inflammation via M2 macrophage polarization; and facilitating collagen deposition. Their antibacterial properties and controlled release of growth factors such as VEGF and TGF-β1 further support tissue regeneration. Additionally, scaffold composition improves mechanical strength, elasticity, and growth factor bioavailability. Innovations such as GelMA/SFMA hydrogels and COL/PRP-ADSC-exos composites have shown superior outcomes in preclinical models.</div></div><div><h3>Conclusions</h3><div>PRP-based scaffolds offer a multifunctional platform for chronic wound treatment by combining biological activity with structural support. Despite existing challenges such as variability in PRP preparation and limited clinical data, ongoing research and emerging technologies hold strong potential to standardize and enhance these therapies for future clinical translation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 278-298"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}