Regenerative Therapy最新文献

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Recombinant production of canine vitronectin for optimizing the culture of canine induced pluripotent stem cells 重组犬玻璃体连接蛋白优化犬诱导多能干细胞培养
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-09-16 DOI: 10.1016/j.reth.2025.09.002
Kohei Shishida , Yui Ikuta , Hiroko Sugisaki , Kazuto Kimura , Jun Katahira , Masaya Tsukamoto , Shingo Hatoya
{"title":"Recombinant production of canine vitronectin for optimizing the culture of canine induced pluripotent stem cells","authors":"Kohei Shishida ,&nbsp;Yui Ikuta ,&nbsp;Hiroko Sugisaki ,&nbsp;Kazuto Kimura ,&nbsp;Jun Katahira ,&nbsp;Masaya Tsukamoto ,&nbsp;Shingo Hatoya","doi":"10.1016/j.reth.2025.09.002","DOIUrl":"10.1016/j.reth.2025.09.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Canine induced pluripotent stem cells (ciPSCs) have attracted attention as valuable tools in veterinary regenerative medicine and disease modeling. Feeder-free culture of ciPSCs using iMatrix-511 has become feasible. Since the choice of extracellular matrix (ECM) has been shown to significantly affect not only the maintenance of pluripotency but also the efficiency of directed differentiation, systematic evaluation of multiple ECM substrates is considered important in ciPSC culture as well. Furthermore, considering future clinical applications, it is essential to establish a xeno-free culture system. Vitronectin (VTN) is a protein that can be easily expressed as a recombinant product in <em>Escherichia coli</em>, making it suitable for scalable ECM production. In this study, we generated recombinant canine-derived VTN and evaluated its effects on ciPSCs in comparison with human-derived ECM substrates.</div></div><div><h3>Methods</h3><div>In this study, we generated recombinant full-length and N-terminally truncated forms of canine vitronectin (cVTN and cVTN-N) using a bacterial expression system. These substrates, along with established human-derived ECM proteins including iMatrix-511, hVTN, and hVTN-N, were evaluated for their ability to support ciPSC adhesion, proliferation, and the maintenance of pluripotency and differentiation potential. Pluripotency and differentiation capacity were assessed using immunostaining and gene expression analysis.</div></div><div><h3>Results</h3><div>Both cVTN and cVTN-N demonstrated support for ciPSC attachment and long-term proliferation at levels comparable to those of human-derived ECM substrates. ciPSCs cultured on cVTN or cVTN-N maintained high expression levels of pluripotency markers; in particular, cVTN significantly enhanced SOX2 expression, while cVTN-N was associated with reduced mesodermal marker expression. Efficient EBs formation and trilineage differentiation were achieved on all tested substrates, with only minor differences in lineage marker expression among groups.</div></div><div><h3>Conclusions</h3><div>Recombinant canine-derived VTN were shown to function as an effective, species-matched substrate for ciPSC culture, exhibiting comparable performance to human-derived ECM proteins. These results suggest that canine-derived VTN enables stable proliferation and maintenance of pluripotency in ciPSCs, providing a promising platform for future research in canine regenerative medicine.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 751-759"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094919","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}
引用次数: 0
Functional analysis of human induced pluripotent stem cell-derived cardiac tissue during endothelial cell network changes 内皮细胞网络变化过程中人诱导多能干细胞衍生心脏组织的功能分析
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-09-10 DOI: 10.1016/j.reth.2025.08.015
Toshiharu Koike , Katsuhisa Matsuura , Shinako Masuda , Takuma Takada , Tatsuro Iida , Tatsuya Shimizu , Junichi Yamaguchi
{"title":"Functional analysis of human induced pluripotent stem cell-derived cardiac tissue during endothelial cell network changes","authors":"Toshiharu Koike ,&nbsp;Katsuhisa Matsuura ,&nbsp;Shinako Masuda ,&nbsp;Takuma Takada ,&nbsp;Tatsuro Iida ,&nbsp;Tatsuya Shimizu ,&nbsp;Junichi Yamaguchi","doi":"10.1016/j.reth.2025.08.015","DOIUrl":"10.1016/j.reth.2025.08.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Tissue structure stability is essential for effective contractile function in cardiac tissue. Although endothelial cells (ECs) serve as critical sources for functional bioengineered cardiac tissue, the process of network changes in ECs affects the cardiac tissue structure. However, how the process precisely influences the synchrony of cardiomyocytes (CMs) contraction and the contraction regularity in the cardiac tissue remains unclear.</div></div><div><h3>Methods</h3><div>Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) were cultured in well-plates for 9–10 days until they displayed stable spontaneous beating. Human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs), or NHDFs alone, were then seeded and cultured with hiPSC-CMs for 3 days (NHDF + HUVEC + CM, NHDF + CM). Changes in the EC network and cardiac functionality were analyzed over the 3-day period following seeding.</div></div><div><h3>Results</h3><div>The EC network expanded until day 2, after which it stabilized. The EC network was observed at the layer of hiPSC-CMs on day 3 in NHDF + HUVEC + CM cultures. Motion capture analysis revealed that hiPSC-CMs in NHDF + HUVEC + CM exhibited more synchronous contractions on day 2 than those in NHDF + CM, with no notable differences on days 1 and 3. The irregularity of spontaneous beat rates, measured using cardiac calcium imaging, was significantly higher in NHDF + HUVEC + CM than in NHDF + CM on day 1. However, the irregularity of spontaneous beating in NHDF + HUVEC + CM was more stabilized on day 3 compared with day1. Other parameters, including contraction amplitude, spontaneous beat rate, and calcium uptake and release, did not significantly differ between NHDF + HUVEC + CM and NHDF + CM over time.</div></div><div><h3>Conclusions</h3><div>Alterations in the EC network may induce irregular spontaneous contractions in hiPSC-CMs at the early phase of co-culture followed by more regular contractions over time, with improving synchrony in the contractions within the cardiac tissue transiently.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 740-750"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044360","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}
引用次数: 0
Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase LATS激酶小分子抑制剂使角膜内皮细胞体外扩增
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-09-03 DOI: 10.1016/j.reth.2025.08.014
Natsuki Abe-Fukasawa , Ryuhei Hayashi , Mio Morita , Shohei Azuma , Takumi Iwawaki , Kenta Kagaya , Taito Nishino , Kohji Nishida
{"title":"Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase","authors":"Natsuki Abe-Fukasawa ,&nbsp;Ryuhei Hayashi ,&nbsp;Mio Morita ,&nbsp;Shohei Azuma ,&nbsp;Takumi Iwawaki ,&nbsp;Kenta Kagaya ,&nbsp;Taito Nishino ,&nbsp;Kohji Nishida","doi":"10.1016/j.reth.2025.08.014","DOIUrl":"10.1016/j.reth.2025.08.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Transplantation of expanded corneal endothelial cells (CECs) has been regarded as a promising approach for treating corneal diseases caused by CEC damage or dysfunction. However, an efficient method for expanding CECs remains inadequately established.</div></div><div><h3>Methods</h3><div>We examined whether small molecule inhibitors of large tumor suppressor kinase (LATS) promote the proliferation of CECs. We also evaluated the expression of functional markers in CECs treated with the inhibitors.</div></div><div><h3>Results</h3><div>We found that LATS kinase inhibitors enhance the cell density of bovine CECs <em>ex vivo</em>. CECs that were expanded in the presence of these inhibitors exhibited increased nuclear translocation of yes-associated protein (YAP) and upregulated expression of YAP-regulated genes. Furthermore, we observed that YAP was essential for promoting cell proliferation. Notably, the inhibitors also increased the density of primary human CECs. Expanded human CECs expressed CEC functional markers, including Na<sup>+</sup>/K<sup>+</sup>-transporting ATPase subunit alpha-1 (ATP1A1), Zonula occludens-1 (ZO-1), and N-cadherin; they showed upregulated expression of YAP-regulated genes.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings support the development of efficient culture techniques for CEC expansion and may facilitate the advancement of therapeutic strategies for CEC-associated diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 730-739"},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932122","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}
引用次数: 0
Cisplatin-induced acute kidney injury is alleviated by BMSCs-derived exosome via mmu-miR-874-3p-mediated activation of the wnt/β-catenin signaling pathway 通过mmu- mir -874-3p介导的wnt/β-catenin信号通路激活,bmscs来源的外泌体减轻了顺铂诱导的急性肾损伤
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-09-01 DOI: 10.1016/j.reth.2025.08.016
Deyang Kong , Zhuohang Yang , Xiaoting Zhang , Yifan Song , Umer Anayyat , Yanping Li , Hao Liu , Zhanci Ou , Shuo Pang , Xiaomei Wang
{"title":"Cisplatin-induced acute kidney injury is alleviated by BMSCs-derived exosome via mmu-miR-874-3p-mediated activation of the wnt/β-catenin signaling pathway","authors":"Deyang Kong ,&nbsp;Zhuohang Yang ,&nbsp;Xiaoting Zhang ,&nbsp;Yifan Song ,&nbsp;Umer Anayyat ,&nbsp;Yanping Li ,&nbsp;Hao Liu ,&nbsp;Zhanci Ou ,&nbsp;Shuo Pang ,&nbsp;Xiaomei Wang","doi":"10.1016/j.reth.2025.08.016","DOIUrl":"10.1016/j.reth.2025.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) results from cisplatin chemotherapeutic agents in 30 %–46 % of patients, but clinically effective preventive and therapeutic approaches are lacking. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) have potential in tissue repair, but the mechanism by which they attenuate cisplatin-induced kidney injury is unknown.</div></div><div><h3>Objective</h3><div>To explore the therapeutic effect of BMSCs-exo on cisplatin-induced AKI and to analyze the key molecular mechanism involved.</div></div><div><h3>Methods and materials</h3><div>BMSCs-exo were extracted via ultracentrifugation and identified via transmission electron microscopy, nanoparticle analysis and Western blot. C57BL/6 mice were divided into a control group (Con), a cisplatin model group (Cis), and a BMSCs-exo treatment group (BMSCs-exo), and renal function was dynamically tested. PAS staining was used to observe histopathological changes in mouse kidney tissues, while immunohistochemistry was employed to assess the expression levels of Wnt4, β-catenin, FZD5, CD31, and the tubular injury markers NGAL and KIM1. Western blot was used to detect the expression of Wnt4, β-catenin, FZD5 and CD31. High-throughput sequencing was used to screen for differential miRNAs, and GO/KEGG enrichment analysis of target genes was performed.</div></div><div><h3>Results</h3><div>Blood creatinine and urea nitrogen levels were significantly higher in the Cis group than in the Con group, and renal tubular epithelial cells exhibited necrosis, confirming successful AKI model establishment. BMSCs-exo alleviated renal dysfunction, histopathological alterations, and tubular injury in vivo, as evidenced by NGAL and KIM1 expression. We further demonstrated that BMSCs-exo specifically localized to the injured kidney. MiRNA sequencing of renal tissues from the Con, Cis and BMSCs-exo groups identified mmu-miR-874-3p—enriched in Wnt signaling and angiogenesis pathways—as a key mediator of the renoprotective effects of BMSCs-exo, with FZD5 as its downstream target. Moreover, treatment with BMSCs-exo markedly prevented microvascular loss. In the BMSCs-exo group, Wnt4, β-catenin and CD31 expression were upregulated, whereas FZD5 expression was downregulated, consistent with the immunohistochemistry results.</div></div><div><h3>Conclusions</h3><div>BMSCs-exo protect kidneys against cisplatin-induced AKI(<em>Cis</em>-AKI) by attenuating injury to the renal microvasculature and tubule epithelial cells, primarily through mmu-miR-874-3p-mediated inhibition of FZD5 activation and promotion of Wnt/β-catenin pathway activation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 719-729"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925616","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}
引用次数: 0
Exosomes derived from platelet-rich plasma promote hair regeneration by regulating the SIRT1/FoxO3a pathway to alleviate oxidative stress 来自富血小板血浆的外泌体通过调节SIRT1/FoxO3a通路促进毛发再生,从而减轻氧化应激
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-25 DOI: 10.1016/j.reth.2025.08.005
Xin Yang , Ke Wang , Guanmao Liu , Yuanju Chen , Ying Wang , Yujing Cheng , Chan Zhang
{"title":"Exosomes derived from platelet-rich plasma promote hair regeneration by regulating the SIRT1/FoxO3a pathway to alleviate oxidative stress","authors":"Xin Yang ,&nbsp;Ke Wang ,&nbsp;Guanmao Liu ,&nbsp;Yuanju Chen ,&nbsp;Ying Wang ,&nbsp;Yujing Cheng ,&nbsp;Chan Zhang","doi":"10.1016/j.reth.2025.08.005","DOIUrl":"10.1016/j.reth.2025.08.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Alopecia is a common disorder that severely affects the mental well-being and quality of life of those affected, yet available treatment options remain limited. Emerging evidence suggests that exosomes from diverse cellular sources possess therapeutic potential for alopecia. However, research on the application of platelet-rich plasma-derived exosomes (PRP-exos) in promoting hair growth is still relatively sparse. This study aims to elucidate the effects of PRP-exos on hair growth and to investigate the associated molecular mechanisms.</div></div><div><h3>Methods</h3><div>We employed conventional molecular biology techniques to evaluate the impacts of PRP-exos on hair follicle stem cells (HFSCs) in terms of proliferation, apoptosis, and migration, as well as their protective effects against oxidative stress. A murine model of alopecia was utilized, and the effectiveness of subcutaneously administered PRP-exos on hair growth was assessed through histological analysis. Additionally, RNA sequencing (RNA-seq) was conducted to explore the potential pathways mediating the effects of PRP-exos on hair growth.</div></div><div><h3>Results</h3><div>Our results demonstrate that PRP-exos significantly enhance both the proliferation and migration of HFSCs while concurrently inhibiting apoptosis and mitigating oxidative stress-induced damage. The subcutaneous injection of PRP-exos fostered hair regeneration in mice, marked by an increase in hair follicle counts of the anagen phase and dermal thickening. Importantly, we found that treatment with PRP-exos upregulated the expression of SIRT1, leading to the deacetylation of FoxO3a and a subsequent reduction in oxidative stress effects.</div></div><div><h3>Conclusions</h3><div>Ultimately, our findings suggest that PRP-exos facilitate hair regeneration by modulating the SIRT1/FoxO3a pathway, providing more evidence for their clinical application in alopecia management.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 710-718"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893482","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}
引用次数: 0
Corrigendum to “Advances in sciatic nerve regeneration: A review of contemporary techniques” [Regen Ther, Volume 29C, (June 2025), 563–574] “坐骨神经再生进展:当代技术回顾”的勘误表[Regen Ther,卷29C,(2025年6月),563-574]
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-23 DOI: 10.1016/j.reth.2025.08.013
Sardar Ali , Ming Sun , Muhammad Nadeem Khan , Fang Qiang
{"title":"Corrigendum to “Advances in sciatic nerve regeneration: A review of contemporary techniques” [Regen Ther, Volume 29C, (June 2025), 563–574]","authors":"Sardar Ali ,&nbsp;Ming Sun ,&nbsp;Muhammad Nadeem Khan ,&nbsp;Fang Qiang","doi":"10.1016/j.reth.2025.08.013","DOIUrl":"10.1016/j.reth.2025.08.013","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Page 691"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889624","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}
引用次数: 0
Harnessing stromal vascular fraction-based therapies for wound healing: Mechanisms, synergies, and clinical translation 利用基质血管分块治疗伤口愈合:机制、协同作用和临床转化
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-22 DOI: 10.1016/j.reth.2025.08.012
Jing Wu , Yao Wang , Wenjie Chen , Min Lin , Jinwen Jiang , Hongde Jiang , Zehuan Li , Kailei Xu , Bin Zhang
{"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":"2025-08-22","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}
引用次数: 0
Microbiome-derived bile acids as endogenous regenerative mediators in liver repair 微生物源胆汁酸作为内源性再生介质在肝脏修复中的作用
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-21 DOI: 10.1016/j.reth.2025.08.011
Surya Nath Pandey , Kavita Goyal , Mohit Rana , Soumya V. Menon , Subhashree Ray , Haider Ali , Popat S. Kumbhar , John Disouza , Sachin Kumar Singh , Gaurav Gupta , Ling Shing Wong , Vinoth Kumarasamy , Vetriselvan Subramaniyan
{"title":"Microbiome-derived bile acids as endogenous regenerative mediators in liver repair","authors":"Surya Nath Pandey ,&nbsp;Kavita Goyal ,&nbsp;Mohit Rana ,&nbsp;Soumya V. Menon ,&nbsp;Subhashree Ray ,&nbsp;Haider Ali ,&nbsp;Popat S. Kumbhar ,&nbsp;John Disouza ,&nbsp;Sachin Kumar Singh ,&nbsp;Gaurav Gupta ,&nbsp;Ling Shing Wong ,&nbsp;Vinoth Kumarasamy ,&nbsp;Vetriselvan Subramaniyan","doi":"10.1016/j.reth.2025.08.011","DOIUrl":"10.1016/j.reth.2025.08.011","url":null,"abstract":"<div><div>The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome-derived bile acid metabolites are potent endogenous mediators of hepatic regeneration. Beyond their canonical role in lipid emulsification, these chemically diverse molecules engage nuclear and membrane receptors, most notably the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to stimulate hepatocyte proliferation, modulate inflammatory responses, and reactivate quiescent progenitor cells. In this review, we integrate mechanistic insights from partial hepatectomy, germ-free, and antibiotic-treated animal models with early clinical observations to illuminate how primary and secondary bile acids orchestrate cell cycle progression, cytokine balance, and extracellular matrix remodeling. We then examined the therapeutic landscape, from synthetic FXR/TGR5 agonists to live-biotherapeutic approaches, genetically modified probiotic strains, and fecal microbiota transplantation. We highlight the preliminary indicators of efficacy and challenges in manufacturing consistency, safety profiling, and regulatory classification. We address the interindividual variability in microbiome composition, potential biomarkers such as serum FGF19, imaging-based measures of functional liver mass, and considerations for optimal trial design. This is the first comprehensive review to frame microbiome-driven bile acids as direct modulators of liver regeneration and chart a coherent translational development pathway. By integrating stem cell biology, hepatology, microbiology, and bioengineering perspectives, we demonstrate the underexplored therapeutic potential of these approaches to transform the future of hepatic repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 681-690"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887218","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}
引用次数: 0
Innovative tissue engineering strategies for auricular regeneration in microtia: Current advances and future perspectives 创新组织工程策略用于耳廓再生:当前进展和未来展望
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-21 DOI: 10.1016/j.reth.2025.08.010
Yu Guo , Zhenghua Huang , Dingyuan Dai , Chen Lu , Mengdi Zou , Chen Sun , Qi Li
{"title":"Innovative tissue engineering strategies for auricular regeneration in microtia: Current advances and future perspectives","authors":"Yu Guo ,&nbsp;Zhenghua Huang ,&nbsp;Dingyuan Dai ,&nbsp;Chen Lu ,&nbsp;Mengdi Zou ,&nbsp;Chen Sun ,&nbsp;Qi Li","doi":"10.1016/j.reth.2025.08.010","DOIUrl":"10.1016/j.reth.2025.08.010","url":null,"abstract":"<div><div>Microtia is a congenital auricular malformation that typically requires reconstructive surgery to restore both form and function. Autologous costal cartilage transplantation remains the clinical standard, yet its invasiveness and donor-site morbidity have driven growing interest in tissue-engineered alternatives. Modern cartilage tissue engineering integrates seed cells, biomaterial scaffolds, and bioactive factors, augmented by emerging technologies such as 3D printing, electrospinning, and dynamic bioreactors. This review summarizes recent progress in auricular reconstruction, with a focus on multilayer scaffold design, diverse cell sources, and advanced bioreactor systems. We emphasize the pivotal role of multi-omics technologies in elucidating the molecular mechanisms underlying chondrogenesis. However, despite substantial progress, clinical translation remains hindered by persistent challenges in replicating the complex architecture of the auricle and achieving long-term stability of engineered cartilage. Optimizing tissue engineering strategies and integrating regenerative medicine with surgical practice may help advance clinical outcomes in microtia treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 665-680"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880052","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}
引用次数: 0
Resolve D1 promotions the repair of cornal epidemiological damage in diabetes by regulating epidemiological response and oxidative stress Resolve D1通过调节流行病学反应和氧化应激促进糖尿病角膜流行病学损伤的修复
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2025-08-20 DOI: 10.1016/j.reth.2025.07.012
Jiayang Xu , Yuanyuan Qi , Ying Zhu , Pengjiao Liu
{"title":"Resolve D1 promotions the repair of cornal epidemiological damage in diabetes by regulating epidemiological response and oxidative stress","authors":"Jiayang Xu ,&nbsp;Yuanyuan Qi ,&nbsp;Ying Zhu ,&nbsp;Pengjiao Liu","doi":"10.1016/j.reth.2025.07.012","DOIUrl":"10.1016/j.reth.2025.07.012","url":null,"abstract":"<div><h3>Objective</h3><div>It aimed to thoroughly analyze the promotive outcome of Resolvin D1 (RvD1) on the repair of corneal epithelium (CE) damage in diabetes mellitus (DM) mice and its molecular mechanisms.</div></div><div><h3>Methods</h3><div>27 male C57BL/6J mice were selected. Type 1 diabetes mellitus(T1DM) mice models were prepared by streptozotocin (STZ) intraperitoneal injection (IPI), and central CE scraping was performed on all mice. They were grouped: Group S1 (S1G, RvD1 treatment), Group S2 (S2G, DM mice), and Group D0 (D0G, normal mice). The CE defect area and sensitivity, the expression of CE regeneration pathway-related factors and oxidative stress (OS) indicators, and the expression of antioxidant genes, inflammatory-related factors were compared.</div></div><div><h3>Results</h3><div>As against S2G, in D0G and S1G, the corneal defect area was visibly smaller at 1, 2, and 3 d post-surgery, and the corneal sensitivity was consistently greater from 1 to 9 d; The content of <em>p</em>-EGFR, Sirt1, Ki67, GSH, Nrf2, MnSOD, NQO-1, and HO-1 in the CE in D0G and S1G was visibly greater as against S2G; As against S2G, in the CE in D0G and S1G, the activity of myeloperoxidase (MPO), the concentration of tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were visibly lower, and the content of reactive oxygen species (ROS), NOX-2, and NOX-4 was visibly smaller (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>RvD1 has been shown to effectively improve corneal repair capabilities in DM mice, alleviate corneal damage, and enhance corneal sensitivity. Its effects may be mediated by regulating factors related to corneal epithelial regeneration, thereby promoting the repair and regeneration of the CE. Additionally, it mitigates OS responses induced by DM, reduces free radical damage, and further facilitates corneal healing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 656-664"},"PeriodicalIF":3.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863986","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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