Pub Date : 2025-12-16DOI: 10.1016/j.reth.2025.101050
Yuxin Liu , Yalu Pu , Qi Li , Liang Yu , Hailong Kou , Yang Liu , Zhizhong Shen , Yilei Zhao
<div><h3>Background</h3><div>Tendon injuries are a common musculoskeletal problem, often leading to chronic pain and disability. Current treatment options, including surgical interventions and physical therapy, have limitations in terms of efficacy and potential complications. Human umbilical cord mesenchymal stem cells (HUCMSCs) are a promising source of mesenchymal stem cells (MSCs), and exosomes derived from HUCMSCs have been shown to mediate various biological processes. This study aims to investigate the role of HUCMSC-derived exosomes in tendon injuries and the underlying mechanism.</div></div><div><h3>Methods</h3><div>Exosomes were isolated from HUCMSCs using differential centrifugation. Cell viability was assessed using a cell counting kit-8 assay. Cell proliferation was measured by a 5-Ethynyl-2′-deoxyuridine assay. Transwell invasion assays were conducted to analyze cell invasion, and wound-healing assays were used to evaluate cell migration. Quantitative real-time PCR (qRT-PCR) was employed to analyze DNM2 mRNA expression. Western blotting was used to detect the protein expression of NOP2/Sun RNA methyltransferase 2 (NSUN2), C cluster of differentiation 63 (CD63), CD81, and dynamin 2 (DNM2). m5C methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays were performed to analyze the association of NSUN2 with DNM2. Additionally, an RIP assay was conducted to study the interaction among Y-box binding protein 1 (YBX1), NSUN2, and DNM2 in injured tenocytes. Rats were subjected to superficial tendon excision and partial transection of the deep Achilles tendon to induce tendon injury. Hematoxylin and eosin (HE) staining was used to analyze the pathological conditions of Achilles tendon tissues, and an immunohistochemistry (IHC) assay was performed to detect the positive expression rates of NSUN2 protein.</div></div><div><h3>Results</h3><div>HUCMSC-derived exosomes significantly promoted the proliferation, migration, and invasion of injured tenocytes. Overexpression of NSUN2 also enhanced the proliferative, migratory and invasive abilities of injured tenocytes. The exosomes derived from NSUN2-overexpressing HUCMSCs showed a more pronounced promoting effect on injured tenocyte proliferation, migration, and invasion compared to control exosomes. NSUN2 stabilized DNM2 mRNA expression through m5C methylation modification. YBX1 interacted with NSUN2 to stabilize DNM2 expression. In addition, knockdown of DNM2 attenuated the promoting effects of HUCMSC-derived exosomes with NSUN2 overexpression on the proliferation, migration, and invasion of injured tenocytes. Moreover, exosomes derived from NSUN2-overexpressing HUCMSCs improved tendon injury in a rat model, as indicated by enhanced pathological conditions within the tendon tissues.</div></div><div><h3>Conclusion</h3><div>HUCMSC-derived exosomal NSUN2 played a crucial role in ameliorating tendon injury by promoting DNM2 expression. The findings suggest that exosomes from NSUN2-ove
{"title":"NSUN2-engineered human umbilical cord mesenchymal stem cell-derived exosomes ameliorate tendon injury by promoting DNM2 expression","authors":"Yuxin Liu , Yalu Pu , Qi Li , Liang Yu , Hailong Kou , Yang Liu , Zhizhong Shen , Yilei Zhao","doi":"10.1016/j.reth.2025.101050","DOIUrl":"10.1016/j.reth.2025.101050","url":null,"abstract":"<div><h3>Background</h3><div>Tendon injuries are a common musculoskeletal problem, often leading to chronic pain and disability. Current treatment options, including surgical interventions and physical therapy, have limitations in terms of efficacy and potential complications. Human umbilical cord mesenchymal stem cells (HUCMSCs) are a promising source of mesenchymal stem cells (MSCs), and exosomes derived from HUCMSCs have been shown to mediate various biological processes. This study aims to investigate the role of HUCMSC-derived exosomes in tendon injuries and the underlying mechanism.</div></div><div><h3>Methods</h3><div>Exosomes were isolated from HUCMSCs using differential centrifugation. Cell viability was assessed using a cell counting kit-8 assay. Cell proliferation was measured by a 5-Ethynyl-2′-deoxyuridine assay. Transwell invasion assays were conducted to analyze cell invasion, and wound-healing assays were used to evaluate cell migration. Quantitative real-time PCR (qRT-PCR) was employed to analyze DNM2 mRNA expression. Western blotting was used to detect the protein expression of NOP2/Sun RNA methyltransferase 2 (NSUN2), C cluster of differentiation 63 (CD63), CD81, and dynamin 2 (DNM2). m5C methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays were performed to analyze the association of NSUN2 with DNM2. Additionally, an RIP assay was conducted to study the interaction among Y-box binding protein 1 (YBX1), NSUN2, and DNM2 in injured tenocytes. Rats were subjected to superficial tendon excision and partial transection of the deep Achilles tendon to induce tendon injury. Hematoxylin and eosin (HE) staining was used to analyze the pathological conditions of Achilles tendon tissues, and an immunohistochemistry (IHC) assay was performed to detect the positive expression rates of NSUN2 protein.</div></div><div><h3>Results</h3><div>HUCMSC-derived exosomes significantly promoted the proliferation, migration, and invasion of injured tenocytes. Overexpression of NSUN2 also enhanced the proliferative, migratory and invasive abilities of injured tenocytes. The exosomes derived from NSUN2-overexpressing HUCMSCs showed a more pronounced promoting effect on injured tenocyte proliferation, migration, and invasion compared to control exosomes. NSUN2 stabilized DNM2 mRNA expression through m5C methylation modification. YBX1 interacted with NSUN2 to stabilize DNM2 expression. In addition, knockdown of DNM2 attenuated the promoting effects of HUCMSC-derived exosomes with NSUN2 overexpression on the proliferation, migration, and invasion of injured tenocytes. Moreover, exosomes derived from NSUN2-overexpressing HUCMSCs improved tendon injury in a rat model, as indicated by enhanced pathological conditions within the tendon tissues.</div></div><div><h3>Conclusion</h3><div>HUCMSC-derived exosomal NSUN2 played a crucial role in ameliorating tendon injury by promoting DNM2 expression. The findings suggest that exosomes from NSUN2-ove","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101050"},"PeriodicalIF":3.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796776","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}
Pub Date : 2025-12-05DOI: 10.1016/j.reth.2025.101046
Yu-Min Chen , Chihoko Tokoda , Yasuhiko Tabata
Cell expansion under three-dimensional (3D) condition has been shown to better preserve cellular properties by mimicking the native microenvironment, thereby creating a more physiologically relevant culture system. This study investigated the capacity of a three-dimensional nonwoven polyethylene terephthalate (PET)/ethylene vinyl alcohol (EVOH) scaffold as a 3D substrate for large-scale expansion of mesenchymal stem cells (MSC). A seven-fold increase in cell number was observed after 14 days of cultivation, and cells were well distributed with an efficient infiltration within scaffolds based on the hematoxylin and eosin (H&E) staining. A high cell survival and pertaining of metabolic activity were demonstrated by live/dead and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) stainings, respectively. The preservation of MSC properties was confirmed by their differentiation potential toward osteogenic, adipogenic, and chondrogenic lineages. Both in situ differentiation of cell-expanded scaffolds and the subsequent differentiation after cell retrieving from scaffolds revealed the successful responsiveness of expanded MSC to lineage-specific stimuli. These findings suggest the potential of this PET/EVOH scaffold as the 3D culture substrate enabling efficient MSC proliferation while maintaining key functional properties.
{"title":"PET/EVOH nonwoven fabrics support in vitro expansion of mesenchymal stem cells with high differentiation potential","authors":"Yu-Min Chen , Chihoko Tokoda , Yasuhiko Tabata","doi":"10.1016/j.reth.2025.101046","DOIUrl":"10.1016/j.reth.2025.101046","url":null,"abstract":"<div><div>Cell expansion under three-dimensional (3D) condition has been shown to better preserve cellular properties by mimicking the native microenvironment, thereby creating a more physiologically relevant culture system. This study investigated the capacity of a three-dimensional nonwoven polyethylene terephthalate (PET)/ethylene vinyl alcohol (EVOH) scaffold as a 3D substrate for large-scale expansion of mesenchymal stem cells (MSC). A seven-fold increase in cell number was observed after 14 days of cultivation, and cells were well distributed with an efficient infiltration within scaffolds based on the hematoxylin and eosin (H&E) staining. A high cell survival and pertaining of metabolic activity were demonstrated by live/dead and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) stainings, respectively. The preservation of MSC properties was confirmed by their differentiation potential toward osteogenic, adipogenic, and chondrogenic lineages. Both <em>in situ</em> differentiation of cell-expanded scaffolds and the subsequent differentiation after cell retrieving from scaffolds revealed the successful responsiveness of expanded MSC to lineage-specific stimuli. These findings suggest the potential of this PET/EVOH scaffold as the 3D culture substrate enabling efficient MSC proliferation while maintaining key functional properties.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101046"},"PeriodicalIF":3.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691063","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}
Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative joint disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling, yet its molecular pathogenesis remains poorly understood. In this study, we investigated the role of proteoglycan 4 (Prg4), also known as lubricin, in maintaining temporomandibular joint (TMJ) homeostasis under physiological and pathological conditions, with the aim of exploring its potential for regenerative therapeutic applications.
Methods
Using high-resolution Visium HD spatial transcriptomics, we examined the spatial distribution of Prg4 expression within the TMJ. To model TMJ-OA, surgically induced anterior disc displacement (ADD) was performed in wild-type (WT) and Prg4-knockout (Prg4-KO) mice. In addition, inflammatory stimulation with IL-1β was applied to synovial cells in vitro. Lineage tracing approaches were used to track Prg4-expressing cells under pathological conditions.
Results
Spatial transcriptomics revealed that Prg4 expression was highly localized to the posterior synovium of the articular disc, with markedly lower expression in anterior regions. While sham-operated TMJs remained histologically intact, the ADD model resulted in condylar deformation, cartilage degeneration, synovial hyperplasia, and subchondral bone loss—phenotypes that were significantly exacerbated in Prg4-KO mice. Furthermore, IL-1β stimulation increased matrix metalloproteinase expression in Prg4-deficient synovial cells. Lineage tracing demonstrated expansion of Prg4-expressing cells within inflamed synovial tissues in the ADD model. Quantitative analysis revealed that Prg4 expression was transiently increased at 2 weeks after ADD induction and returned to control levels by 8 weeks, indicating a time-dependent regulatory role during inflammation.
Conclusion
These findings highlight the region-specific and time-dependent function of Prg4 in the TMJ and underscore its critical role in suppressing joint inflammation and degeneration. Importantly, our results suggest that modulation of Prg4 expression or lubricin supplementation could serve as a regenerative therapeutic strategy for preserving TMJ homeostasis and preventing chronic degenerative progression, providing a promising avenue for clinical translation in TMJ-OA treatment.
{"title":"Lubricin maintains temporomandibular joint homeostasis by regulating synovial inflammation","authors":"Soichiro Negishi , Kazuhiro Shibusaka , Miki Maemura , Masayuki Tsukasaki , Seigo Ohba , Sakae Tanaka , Taku Saito , Yutaka Suzuki , Hiroyuki Okada , Fumiko Yano","doi":"10.1016/j.reth.2025.101051","DOIUrl":"10.1016/j.reth.2025.101051","url":null,"abstract":"<div><h3>Introduction</h3><div>Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative joint disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling, yet its molecular pathogenesis remains poorly understood. In this study, we investigated the role of proteoglycan 4 (<em>Prg4</em>), also known as lubricin, in maintaining temporomandibular joint (TMJ) homeostasis under physiological and pathological conditions, with the aim of exploring its potential for regenerative therapeutic applications.</div></div><div><h3>Methods</h3><div>Using high-resolution Visium HD spatial transcriptomics, we examined the spatial distribution of <em>Prg4</em> expression within the TMJ. To model TMJ-OA, surgically induced anterior disc displacement (ADD) was performed in wild-type (WT) and <em>Prg4</em>-knockout (Prg4-KO) mice. In addition, inflammatory stimulation with IL-1β was applied to synovial cells <em>in vitro</em>. Lineage tracing approaches were used to track <em>Prg4</em>-expressing cells under pathological conditions.</div></div><div><h3>Results</h3><div>Spatial transcriptomics revealed that <em>Prg4</em> expression was highly localized to the posterior synovium of the articular disc, with markedly lower expression in anterior regions. While sham-operated TMJs remained histologically intact, the ADD model resulted in condylar deformation, cartilage degeneration, synovial hyperplasia, and subchondral bone loss—phenotypes that were significantly exacerbated in Prg4-KO mice. Furthermore, IL-1β stimulation increased matrix metalloproteinase expression in <em>Prg4</em>-deficient synovial cells. Lineage tracing demonstrated expansion of <em>Prg4</em>-expressing cells within inflamed synovial tissues in the ADD model. Quantitative analysis revealed that <em>Prg4</em> expression was transiently increased at 2 weeks after ADD induction and returned to control levels by 8 weeks, indicating a time-dependent regulatory role during inflammation.</div></div><div><h3>Conclusion</h3><div>These findings highlight the region-specific and time-dependent function of <em>Prg4</em> in the TMJ and underscore its critical role in suppressing joint inflammation and degeneration. Importantly, our results suggest that modulation of <em>Prg4</em> expression or lubricin supplementation could serve as a regenerative therapeutic strategy for preserving TMJ homeostasis and preventing chronic degenerative progression, providing a promising avenue for clinical translation in TMJ-OA treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101051"},"PeriodicalIF":3.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691008","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}
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms.
Methods
A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&E staining and serum biochemical markers.
Results
QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and p-CREB/CREB expressions in QZP-treated mice. No hepatic or renal toxicity was detected.
Conclusion
QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair.
{"title":"Qianzheng powder promotes facial nerve regeneration via BDNF/TrkB/CREB pathway activation","authors":"Liang Chen, Chaoqun Wang, Lixin Jiang, Qiang Xie, Hongru Qin, Ziheng Zhang","doi":"10.1016/j.reth.2025.101048","DOIUrl":"10.1016/j.reth.2025.101048","url":null,"abstract":"<div><h3>Introduction</h3><div>Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms.</div></div><div><h3>Methods</h3><div>A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&E staining and serum biochemical markers.</div></div><div><h3>Results</h3><div>QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and <em>p</em>-CREB/CREB expressions in QZP-treated mice. No hepatic or renal toxicity was detected.</div></div><div><h3>Conclusion</h3><div>QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101048"},"PeriodicalIF":3.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691062","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}
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.
Methods
Histological and gene expression differences were analyzed in thyroids of retired rats (>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.
Results
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.
Conclusions
Mismatch between donor thyroid maturity and recipient age may influence engraftment in rat allogenic thyroid transplantation.
{"title":"Influence of donor–recipient age differences in allogenic rat thyroid transplantation","authors":"Ayumi Arauchi , Katsuhisa Matsuura , 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 (>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":"2025-12-01","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}
Pub Date : 2025-11-30DOI: 10.1016/j.reth.2025.101049
Binbin Zhang, Chuan Lu, Bin Dou, Wenzuo Gu, Kewen Li
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
{"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, Chuan Lu, Bin Dou, Wenzuo Gu, 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":"2025-11-30","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}
Pub Date : 2025-11-26DOI: 10.1016/j.reth.2025.11.003
Jia Zhang , Yali Yang , Shuilan Bao , Yiren Wang , Zhongjian Wen , Shouying Chen , Li Yao , Ping Zhou , Yun Zhou , Ying Chen
Purpose
This bibliometric study, based on 1,030 publications from the Web of Science Core Collection through December 31, 2024, explores the evolving landscape of conductive hydrogels in medicine.
Methods
This study uses tools like Bibliometrix, VOSviewer, and CiteSpace to investigate the research hotspots, collaborative patterns, and developmental trends of conductive hydrogels in the medical field from 2015 to 2024, thereby offering novel insights for future research in this domain.
Results
The analysis reveals a significant 38.04 % annual growth rate in publications since 2015. China leads in research output with 734 articles, followed by Korea. Key institutions, including Chinese Academy of Sciences, Sichuan University, and Xi'an Jiaotong University, have been instrumental in driving this field forward. Research hotspots, centered on high-performance scaffolds, are expanding into two main areas: synergistic tissue regeneration and drug delivery, and flexible, wearable point-of-care diagnostics. A key trend is the shift in focus from the hydrogel's material and structure (support, conductivity) to its performance and function (integrated mechanics, sensing, and wearability). This highlights the multidisciplinary potential of conductive hydrogels. Despite China's high publication volume, the study emphasizes that it requires deeper fundamental research and stronger international collaborations.
Conclusions
Future initiatives must emphasize the advancement of multifunctional hydrogel platforms, cultivate interdisciplinary collaborations integrating materials science, medicine, and engineering, and implement consistent preclinical assessment and regulatory frameworks. These strategic steps are crucial for moving hydrogel innovations from the lab to clinical applications, such as chronic wound healing, myocardial repair, and wearable diagnostics.
本文献计量学研究基于Web of Science核心馆藏的1030份出版物，截至2024年12月31日，探讨了导电水凝胶在医学领域的发展前景。方法利用Bibliometrix、VOSviewer、CiteSpace等工具，对2015 - 2024年导电水凝胶在医学领域的研究热点、协同模式和发展趋势进行分析，为今后的研究提供新的思路。结果分析显示，2015年以来，论文发表量年均增长38.04%。中国以734篇论文居首位，其次是韩国。包括中国科学院、四川大学和西安交通大学在内的重点机构在推动该领域的发展方面发挥了重要作用。以高性能支架为中心的研究热点正在扩展到两个主要领域：协同组织再生和药物输送，以及灵活、可穿戴的即时诊断。一个关键趋势是从水凝胶的材料和结构（支撑力、导电性）转向其性能和功能（综合力学、传感和可穿戴性）。这突出了导电水凝胶的多学科潜力。尽管中国的论文发表量很高，但该研究强调，这需要更深入的基础研究和更强有力的国际合作。未来的举措必须强调多功能水凝胶平台的进步，培养材料科学、医学和工程的跨学科合作，并实施一致的临床前评估和监管框架。这些战略步骤对于将水凝胶创新从实验室转移到临床应用至关重要，例如慢性伤口愈合，心肌修复和可穿戴诊断。
{"title":"Mapping the evolving landscape of conductive hydrogels in medicine: A bibliometric perspective","authors":"Jia Zhang , Yali Yang , Shuilan Bao , Yiren Wang , Zhongjian Wen , Shouying Chen , Li Yao , Ping Zhou , Yun Zhou , Ying Chen","doi":"10.1016/j.reth.2025.11.003","DOIUrl":"10.1016/j.reth.2025.11.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This bibliometric study, based on 1,030 publications from the Web of Science Core Collection through December 31, 2024, explores the evolving landscape of conductive hydrogels in medicine.</div></div><div><h3>Methods</h3><div>This study uses tools like Bibliometrix, VOSviewer, and CiteSpace to investigate the research hotspots, collaborative patterns, and developmental trends of conductive hydrogels in the medical field from 2015 to 2024, thereby offering novel insights for future research in this domain.</div></div><div><h3>Results</h3><div>The analysis reveals a significant 38.04 % annual growth rate in publications since 2015. China leads in research output with 734 articles, followed by Korea. Key institutions, including Chinese Academy of Sciences, Sichuan University, and Xi'an Jiaotong University, have been instrumental in driving this field forward. Research hotspots, centered on high-performance scaffolds, are expanding into two main areas: synergistic tissue regeneration and drug delivery, and flexible, wearable point-of-care diagnostics. A key trend is the shift in focus from the hydrogel's material and structure (support, conductivity) to its performance and function (integrated mechanics, sensing, and wearability). This highlights the multidisciplinary potential of conductive hydrogels. Despite China's high publication volume, the study emphasizes that it requires deeper fundamental research and stronger international collaborations.</div></div><div><h3>Conclusions</h3><div>Future initiatives must emphasize the advancement of multifunctional hydrogel platforms, cultivate interdisciplinary collaborations integrating materials science, medicine, and engineering, and implement consistent preclinical assessment and regulatory frameworks. These strategic steps are crucial for moving hydrogel innovations from the lab to clinical applications, such as chronic wound healing, myocardial repair, and wearable diagnostics.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101038"},"PeriodicalIF":3.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622030","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}
Mesenchymal stem cells (MSCs) and their exosome (MSCs-Exos) have been shown to be major therapeutic candidates in regenerative medicine due to their inherent capacity for modulating immune response, promoting angiogenesis, and repairing tissues. However, clinical application of MSCs and MSCs-Exos is hindered by various intrinsic barriers, such as poor survival of transplanted MSCs, quick systemic clearance of exosomes, uncontrolled release of therapeutic payloads, and loss of function in severe pathological situations, such as chronic wounds and fibrotic tissues. To overcome these limitations, recent advances have focused on the design of modern delivery systems to enhance the stability, bioavailability, and functionality of MSCs and MSCs-Exos. These platforms include responsive hydrogels, engineered nanoparticles, and multi responsive intelligent dressings that mirror protective microenvironments in general and provide controlled, long-term distribution of bioactive elements. This current review focuses on such innovative approaches that enhance regeneration results in strong preclinical models, maximize therapeutic delivery, and boost MSCs and exosome survival. Despite remarkable advancements, major obstacles still exist, such as guaranteeing biosafety, achieving scale production, and obtaining regulatory approvals. The combination of MSCs and MSCs-Exos therapies with intelligent, responsive biomaterials capable of providing antimicrobial function and active monitoring has the potential to revolutionize tissue regeneration and wound healing and make MSCs and MSCs-Exos invaluable resources in precision regenerative medicine of the future.
{"title":"Smart integrated biomaterial systems for precision and optimized delivery of MSCs and their exosomes: Transforming wound healing and organ regeneration","authors":"Fatemeh Rafati , Zeynab Ghorbani , Tahereh Manoochehrabadi , Farbod Khosravi , Jila Majidi , Fatemeh Eskandari , Mohamad Eftekhary , Hajar Nasiri","doi":"10.1016/j.reth.2025.101045","DOIUrl":"10.1016/j.reth.2025.101045","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) and their exosome (MSCs-Exos) have been shown to be major therapeutic candidates in regenerative medicine due to their inherent capacity for modulating immune response, promoting angiogenesis, and repairing tissues. However, clinical application of MSCs and MSCs-Exos is hindered by various intrinsic barriers, such as poor survival of transplanted MSCs, quick systemic clearance of exosomes, uncontrolled release of therapeutic payloads, and loss of function in severe pathological situations, such as chronic wounds and fibrotic tissues. To overcome these limitations, recent advances have focused on the design of modern delivery systems to enhance the stability, bioavailability, and functionality of MSCs and MSCs-Exos. These platforms include responsive hydrogels, engineered nanoparticles, and multi responsive intelligent dressings that mirror protective microenvironments in general and provide controlled, long-term distribution of bioactive elements. This current review focuses on such innovative approaches that enhance regeneration results in strong preclinical models, maximize therapeutic delivery, and boost MSCs and exosome survival. Despite remarkable advancements, major obstacles still exist, such as guaranteeing biosafety, achieving scale production, and obtaining regulatory approvals. The combination of MSCs and MSCs-Exos therapies with intelligent, responsive biomaterials capable of providing antimicrobial function and active monitoring has the potential to revolutionize tissue regeneration and wound healing and make MSCs and MSCs-Exos invaluable resources in precision regenerative medicine of the future.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101045"},"PeriodicalIF":3.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622029","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}
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.
{"title":"Decellularized corneal-based 3D scaffolds: methods decellularization, characterization, mechanical properties, and species source","authors":"Vahid Akbaripour , Leila Rezaei , Gelavizh Rostaminasab , Farid Daneshgar , Omid Bahiraee , 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":"2025-11-20","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}
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 in vitro and in vivo outcomes.
Method
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. In vivo 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.
Results
Butyrate preconditioning upregulated angiogenesis- and immune-related genes, including CXCL8, SOD2, and TGM2. It increased IL-10, CXCL5, and MMP-1 secretion. In vitro, 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. In vivo, ASC-BA-CM promoted vascularization and macrophage accumulation in sponges and significantly improved myocardial perfusion by approximately 32 % compared with controls.
Conclusions
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.
脂肪源性干细胞条件培养基（ASC-CM）有望通过旁分泌机制进行心脏修复。然而，疗效的可变性限制了其临床应用。我们研究了用丁酸盐（ASC- ba - cm）预处理人ASC是否能增强其旁分泌效力并改善体外和体内结果。方法对经丁酸处理的人ASCs进行rna测序，以表征转录组学变化。收集CM并通过细胞因子/趋化因子阵列进行分析。使用人脐静脉内皮细胞（HUVECs）进行伤口愈合试验，与THP-1巨噬细胞共培养和不共培养，以评估内皮修复及其与分泌因子的相关性。采用海绵植入模型评估体内血管生成，采用单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）铊-201成像测量大鼠心肌梗死模型的心肌灌注。结果丁酸预处理上调血管生成和免疫相关基因，包括CXCL8、SOD2和TGM2。增加IL-10、CXCL5和MMP-1的分泌。体外，ba预处理的ASC-CM可增强HUVEC伤口愈合，与THP-1巨噬细胞共培养可改善伤口愈合，并与TGFb3和TIMP-2水平呈负相关。在体内，与对照组相比，ASC-BA-CM促进海绵血管化和巨噬细胞积聚，显著改善心肌灌注约32%。结论丁酸预处理可增强大鼠ASC-CM旁分泌活性，并与心肌灌注改善有关。这些发现提示丁酸盐可能增强ASC分泌组功能。潜在的机制如内皮修复、血管生成和免疫调节仍然是假设的，需要在未来的研究中进一步验证。
{"title":"Butyrate-preconditioned human adipose-derived stem cell-conditioned medium enhances myocardial perfusion after infarction","authors":"Shinji Kobuchi , Wan-Tseng Hsu , Misaki Matsuzawa , Rina Kagawa , Junko Watanabe , Koki Harada , Yuki Toda , Shohei Hamada , Masayuki Tsujimoto , Hidekazu Kawashima , Kaneyasu Nishimura , Kenjiro Matsumoto , 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":"2025-11-19","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}
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