Regenerative TherapyPub Date : 2025-12-01Epub Date: 2025-07-30DOI: 10.1016/j.reth.2025.07.002
Yang Shao , Mei Han , Guodong Song , Cong Gao
{"title":"Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair","authors":"Yang Shao , Mei Han , Guodong Song , Cong Gao","doi":"10.1016/j.reth.2025.07.002","DOIUrl":"10.1016/j.reth.2025.07.002","url":null,"abstract":"<div><h3>Objective</h3><div>Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing.</div></div><div><h3>Methods</h3><div>ADSCs were isolated from adipose tissue, characterized via CD marker expression, and confirmed for multipotency using Oil Red O (adipogenesis), Alizarin Red S (osteogenesis), and Alcian Blue staining (chondrogenesis). ADSCs were then transduced with a lentiviral vector carrying HGH, generating HGH-ADSCs and confirmed by qRT-PCR. Fibroblasts (HDF-a) were co-cultured were co-cultured under HGH-ADSCs-conditioned medium and ADSCs-conditioned medium to assess proliferation (MTT assay), migration and invasion (Transwell), apoptosis (flow cytometry), and G0/G1 cell cycle progression. Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency. A burn rat model was established with three treatment groups: HGH-ADSCs, ADSCs, and saline. and histopathology (H&E, TUNEL staining) analyzed epithelial regeneration and apoptosis. ELISA and biochemical assays quantified TNF-α, IL-1β, IL-6, MDA, SOD, and CAT in wound tissue homogenates.</div></div><div><h3>Results</h3><div>HGH-ADSCs significantly enhanced fibroblast proliferation, migration, invasion, and prolonged G0/G1 phase while reducing apoptosis (P < 0.05). ERK inhibition abolished these effects (P < 0.05). In vivo, HGH-ADSCs accelerated wound closure (P < 0.05), enhanced epithelialization, reduced inflammation, and increased collagen formation. Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P < 0.05).</div></div><div><h3>Conclusion</h3><div>ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 465-475"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724655","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":"NN15-017 promotes human pluripotent stem cell proliferation and generation","authors":"Shizuka Fujigaki-Yamazaki , Ryoko Nakatani , Osamu Hirata , Koichiro Saruhashi , Mai Fujii , Hirofumi Suemori , Taito Nishino , Eihachiro Kawase","doi":"10.1016/j.reth.2025.09.003","DOIUrl":"10.1016/j.reth.2025.09.003","url":null,"abstract":"<div><h3>Introduction</h3><div>The nutrient requirements for culturing human pluripotent stem cells (hPSCs) have been studied in relation to the development of chemically defined media. Most hPSC media contain FGF2, which is critical for hPSC growth and maintenance. Here, we investigated compounds that could substitute for FGF2 activity.</div></div><div><h3>Methods</h3><div>To identify compounds that can replace FGF2 and promote the proliferation of undifferentiated hPSCs, we screened our compound library using the hOCT4-EGFP reporter system and evaluated candidates using cell morphological analysis and OCT4 immunostaining as a marker of undifferentiated cells. We further evaluated the extent to which the selected compound can replace FGF2 through long-term culture (over 10 passages). We examined whether the compounds promote the reprogramming efficiency of somatic cells into induced pluripotent stem cells (iPSCs) using mRNA reprogramming. We also analyzed which signaling pathways were activated by the compound using western blotting.</div></div><div><h3>Results</h3><div>We identified a new compound, NN15-017, which enables a reduced concentration of FGF2 in the medium by 5-fold and enhances the reprogramming efficiency of human induced PSCs by 2- to 3-fold. NN15-017 promoted the MAP/ERK signaling pathway downstream of FGF2 and may affect the Hippo-YAP signaling pathway in hPSCs.</div></div><div><h3>Conclusions</h3><div>NN15-017 reduces the requirement for FGF2, thereby providing novel and valuable benefits for the proliferation and generation of human induced PSCs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 838-848"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219349","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":"Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval","authors":"Kenichi Kimura , Kojiro Imai , Morio Ueno , Chie Sotozono","doi":"10.1016/j.reth.2025.07.003","DOIUrl":"10.1016/j.reth.2025.07.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Recently, significant progress has been made in the field of regenerative medicine in Japan for the treatment of ophthalmic diseases, with a notable emphasis placed on clinical research and practical applications, and in 2014, one significant development was the initiation of the world's first clinical research using iPS cells for age-related macular degeneration. In addition, three regenerative medical products for the treatment of limbal stem cell deficiency, a rare and intractable ocular surface disease, have recently been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act). In order to expedite the practical implementation of regenerative medicine, the PMD Act presented a new category for regenerative medical products alongside the two categories that currently exist (i.e., 'pharmaceutical products' and 'medical devices'). However, within the current official Japanese national insurance coverage plan, there is no category designated for 'regenerative medical products'. Although the approval system for regenerative medical products differs from country to country (i.e., the United States Food and Drug Administration (U.S. FDA), the European Medicines Agency (EMA), etc.), in Japan, they are approved by the Japanese MHLW and PMDA. When manufacturers seek newly approved regenerative medical products in Japan to be incorporated within those listed in the Japanese national insurance coverage plan, the products are classified as either 'pharmaceutical products' or 'medical devices' and are reviewed by the Central Social Insurance Medical Council (\"Chuikyo\", in Japanese) of the Japanese MHLW. Although the responsibility for applying for regulatory approval and insurance coverage lies with the manufacturer, as the developer who conducted the clinical study and the investigator-initiated clinical trial for two ophthalmic regenerative medical products (i.e., Sakracy® and Vyznova®), we perceived that the period from regulatory approval to insurance coverage listing for these two products was longer than for other ophthalmic regenerative medical products. These experiences became the research question and the focus was on ophthalmic regenerative medical products, with the rationale behind this submission being that the dissemination of our experience will be of benefit to all clinical researchers and manufacturers. Hence, the purpose of this present study was to investigate the insurance coverage of regenerative medical products for ophthalmic diseases in Japan from the aspect of specific coverage-related categories.</div></div><div><h3>Methods</h3><div>In this study, we investigated newly approved regenerative medical products for ophthalmic diseases in Japan after the Revised Pharmaceutical Affairs Act came into effect in 2014. The insurance coverage ","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 384-388"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604785","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 TherapyPub Date : 2025-12-01Epub Date: 2025-07-26DOI: 10.1016/j.reth.2025.07.006
Qianying Feng , Fengxia Chen , Rui Liu , Dan Li , Huigen Feng , Junzheng Yang
{"title":"Mesenchymal stem cell application in Alzheimer's disease","authors":"Qianying Feng , Fengxia Chen , Rui Liu , Dan Li , Huigen Feng , Junzheng Yang","doi":"10.1016/j.reth.2025.07.006","DOIUrl":"10.1016/j.reth.2025.07.006","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a type of degenerative disease that primarily affects in the central nervous system of elderly or pre-elderly individuals. The symptoms of Alzheimer's disease include memory impairment, aphasia, loss of function, dementia, and impairment of visual spatial ability, which in turn affects the physical health of patients. Mesenchymal stem cell therapy is a branch of regenerative medicine that primarily utilizes stem cells or their derivatives to stimulate the body's own healing process and repair damaged, diseased, or injured tissues. Its utilization in the treatment of autoimmune diseases and neurological disorders has been extensively documented. This review summarizes the preclinical and clinical applications of mesenchymal stem cells in AD, their underlying mechanisms and the application limitations of their application and potential solutions. It is hoped that researchers in this field will find it a useful foundation for further study of mesenchymal stem cell therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 439-445"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713232","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":"Stem/progenitor cell dynamics during salivary gland development and regeneration demonstrated by the double pulse-chase paradigm","authors":"Shusuke Ohshima , Angela Quispe-Salcedo , Hiroko Ida-Yonemochi , Yushi Ueki , Arata Horii , Hayato Ohshima","doi":"10.1016/j.reth.2025.08.007","DOIUrl":"10.1016/j.reth.2025.08.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Active and quiescent stem cells coexist in hair follicles and intestinal crypts; however, their localization and differentiation potential in the salivary dynamics are unknown. This study aimed to clarify the cellular dynamics that occur during salivary gland development and regeneration in the duct ligation model with a focus on the role of label retaining cells (LRCs), presumably quiescent stem cells, in these processes.</div></div><div><h3>Methods</h3><div>Doxycycline-inducible TetOP-histone 2B (H2B)-green fluorescent protein (GFP) transgenic mice [GFP expression was induced during embryonic day 15 (E15)–postnatal day 7 (P7)] followed by EdU (5-ethynyl-2′-deoxyuridine) administration at P10–14 to chase the LRCs during development. In addition, LRCs were labeled with GFP immediately before salivary gland duct ligation and EdU was administered after the ligation was released to chase the LRCs with GFP and EdU during tissue repair.</div></div><div><h3>Results and conclusions</h3><div>During development, GFP (+) EdU (−) LRCs were abundant in striated duct cells (SDCs) and GFP (+) EdU (+) LRCs were primarily localized to the intercalated duct cells (IDCs) at P21. Labeling of the GFP (+) LRCs faded as well as the EdU (+) LRCs at P70. During tissue repair, GFP (+) EdU (+) LRCs were colocalized in the IDCs and myoepithelium cells (MECs), whereas the GFP (+) EdU (+) acinar cells (ACs) appeared over time. These results suggest that salivary gland quiescent stem/progenitor cells are present in the IDCs during development and that quiescent stem/progenitor cells in the IDCs and MECs differentiate into ACs during tissue repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 595-605"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828643","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 TherapyPub Date : 2025-12-01Epub Date: 2025-07-11DOI: 10.1016/j.reth.2025.06.014
Jing Ning, Feng Li, Zhi Xin Pei, Zhi Li
{"title":"Fabrication of Piezo1 protein encapsulated pressure-sensitive multifunctional hydrogel in modulating cellular response and wound healing in pressure ulcer conditions","authors":"Jing Ning, Feng Li, Zhi Xin Pei, Zhi Li","doi":"10.1016/j.reth.2025.06.014","DOIUrl":"10.1016/j.reth.2025.06.014","url":null,"abstract":"<div><div>Pressure ulcers (PUs) are prevalent skin lesions characterized by significant morbidity, susceptibility to infection, and a complex healing process. This study aims at the synthesis of piezo1 protein-encapsulated, pressure-sensitive multifunctional hydrogel to modulate cellular response and promote wound healing in PUW conditions. The hydrogel synthesized from carboxyl methyl cellulose hydrogel exhibits the optimal swelling ratio and is found to have a high storage modulus (G′). This shows the mechanical strength and viscoelastic nature of the synthesized hydrogel. The PP encapsulation and releasing efficiency has been analyzed, and this proves the prolonged activation of mechanotransduction properties. <em>In vitro</em> analysis on 3T3 and HUVEC proves a high proliferation rate and proves to have an enhanced cell migration rate in hypoxia-induced cell lines. The angiogenesis was also found to be increased, which is indicated by tube formation that enhances the wound healing rate. The pressure ulcer animal model was analyzed for 3, 7, 10, and 14 days, and the wound healing rate. The reduction in inflammatory cytokine expression and the collagen deposition rate has been analyzed. By day 14, the wound closure reached above 91%, significantly higher than the untreated group. These findings demonstrate that PP-MH enhances cell proliferation and angiogenesis, thereby acts as a promising strategy for advanced pressure ulcer management.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 371-383"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596716","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 TherapyPub Date : 2025-12-01Epub Date: 2025-10-29DOI: 10.1016/j.reth.2025.10.010
Lu-Hang Xu , Li-Tian Ye , Jia-Yu Wang , Xuan Qiu
{"title":"Magnesium-based alloys for bone regeneration and beyond: A review of advances and therapeutic prospects","authors":"Lu-Hang Xu , Li-Tian Ye , Jia-Yu Wang , Xuan Qiu","doi":"10.1016/j.reth.2025.10.010","DOIUrl":"10.1016/j.reth.2025.10.010","url":null,"abstract":"<div><h3>Background</h3><div>Magnesium (Mg)-based alloys have gained significant attention as next-generation biodegradable biomaterials due to their bone-mimetic mechanical properties (elastic modulus: 35–45 GPa), biocompatibility, and ability to degrade in vivo without toxic byproducts.</div></div><div><h3>Objective</h3><div>This review systematically evaluates recent advances in Mg-based alloys for biomedical applications, focusing on orthopedic implants, cardiovascular stents, and drug delivery systems, while identifying current challenges and future research directions.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature analysis of peer-reviewed studies (2019–2024) examining Mg alloy development, surface modification techniques, in vitro/in vivo performance, and clinical trial outcomes.</div></div><div><h3>Results</h3><div>Key findings include: (1) Alloying innovations, particularly with rare-earth elements (e.g., in WE43) and nutrient elements (Zn, Ca), have yielded alloys with bone-mimetic mechanical properties (elastic modulus: 35–45 GPa; compressive yield strength: 150–250 MPa) and decelerated degradation rates via grain refinement and secondary phase formation; (2) Surface-modified Mg stents show improved endothelialization with 30–50 % reduced restenosis rates (3) Structurally engineered Mg-based scaffolds (e.g., via additive manufacturing); enable topological control over degradation through tailored porosity; (4) Drug-eluting Mg carriers achieve sustained release kinetics, leveraging degradation to simultaneously promote tissue regeneration and deliver therapeutics. However, rapid degradation (0.2–0.5 mm/year in physiological conditions) and hydrogen gas evolution remain critical challenges.</div></div><div><h3>Conclusion</h3><div>Mg-based alloys show transformative potential for temporary medical implants. Future research should focus on: (1) advanced alloy design with rare-earth elements, (2) smart coating technologies, and (3) standardized long-term biocompatibility assessments to facilitate clinical translation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 977-983"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415478","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 TherapyPub Date : 2025-12-01Epub Date: 2025-05-17DOI: 10.1016/j.reth.2025.04.020
Lei Yu , Zihao Dai , Yuchen Huang , Shuo Tang , Lihong Zhou , Xuying Zhao , Xianfeng Que , Rongfeng Shi , Jin Zhou , Jixuan Dong , Feng Wang , Yunjuan Gu
{"title":"A temperature-sensitive chitosan hydrogels loaded with nano-zinc oxide and exosomes from human umbilical vein endothelial cells accelerates wound healing","authors":"Lei Yu , Zihao Dai , Yuchen Huang , Shuo Tang , Lihong Zhou , Xuying Zhao , Xianfeng Que , Rongfeng Shi , Jin Zhou , Jixuan Dong , Feng Wang , Yunjuan Gu","doi":"10.1016/j.reth.2025.04.020","DOIUrl":"10.1016/j.reth.2025.04.020","url":null,"abstract":"<div><div>The suboptimal therapeutic outcomes of diabetic foot ulcers (DFUs) represent a significant global challenge. In recent years, studies have indicated that novel dressings incorporating exosomes (Exos), nanomaterials, and hydrogels following debridement can synergistically promote tissue repair, which has been widely recognized as a promising emerging trend in the treatment of DFUs. In this study, a combination of zinc oxide nanoparticles (ZnO-NPs), Exos, and chitosan (CS) hydrogel (CS/ZnO-NPs@Exos) was applied to the full-thickness cutaneous defects in a diabetic rat model. This CS/ZnO-NPs@Exos hydrogel was applied to the wound site to achieve sustained and long-term release of Exos, allowing the evaluation of its therapeutic effects. This hydrogel significantly improved the wound closure rate in diabetic skin injuries and reduced oedema, erythema and inflammatory exudate at the wound site. These effects were characterized by enhanced re-epithelialization, reduced infiltration of inflammatory cells, increased collagen deposition, and enhanced angiogenesis in the wound area. This may be related to the Exos derived from human umbilical vein endothelial cells (HUVECs), which notably promote the migration and proliferation of fibroblasts. As a result, the CS/ZnO-NPs@Exos hydrogel offers a new therapeutic dressing for the management of diabetic wounds, with the potential to play a crucial role in clinical practice.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 63-74"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071546","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":"Functional analysis of human induced pluripotent stem cell-derived cardiac tissue during endothelial cell network changes","authors":"Toshiharu Koike , Katsuhisa Matsuura , Shinako Masuda , Takuma Takada , Tatsuro Iida , Tatsuya Shimizu , 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":"2025-12-01","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}
{"title":"Stem cell therapy for urethra and ureter tissue engineering: A systematic literature review on animal studies","authors":"Hamoon Baghaei , Ali Faegh , Shima Jahani , Pooya Hekmati , Masoumeh Majidi Zolbin","doi":"10.1016/j.reth.2025.05.001","DOIUrl":"10.1016/j.reth.2025.05.001","url":null,"abstract":"<div><div>The present study investigates the optimal stem cells for using in ureter and urethra tissue engineering by systematically reviewing the literature. Scopus, PubMed, and Embase databases were searched up to December 2024 to find original studies investigating ureter and urethra tissue engineering by seeding stem cells on the scaffolds in animal models, which resulted in the identification of 1191 studies. Finally, 26 studies were included. Eighteen and eight studies tried urethra and ureter tissue regeneration, respectively. Adipose-derived stem cells were the most commonly used for tissue engineering of the ureter and urethra, with 14 studies. Bone marrow-derived stem cells were involved in 5 studies, urine-derived in 3, muscle-derived stem/precursor cells in 3, and human amniotic membrane-derived mesenchymal stem cells in 1. Bladder acellular matrix, artery extracellular matrix, and small intestinal submucosa were non-synthetic seeded scaffolds that were used in 10 studies. However, studies used biomaterial and synthetic scaffolds, including Poly (<span>l</span>-lactide-co-caprolactone) nano yarn, Poly-glycolic acid, nanofiber, double-modified sulfated bacterial cellulose, and silk scaffold more frequently. Data demonstrated that adipose-derived, bone marrow-derived, urine-derived, and human amniotic membrane-derived stem cells have the capability of both urothelium and smooth muscle regeneration in urethra reconstruction. Furthermore, seeding bone marrow-derived stem cells can improve collagen and vessel formation. Also, this study showed that the muscle-derived SCs or precursor cells are able to regenerate urethra smooth muscle, but data are limited. Hypoxia precondition, subcutaneous or omental pre-incubation, fibroblast growth factor receptor Ⅱ overexpression, and mechanical extension stimulation were employed as boosting conditions. However, data about ureter tissue engineering are limited. Adipose-derived stem cells were the most frequently employed for ureter tissue regeneration, with appropriate outcomes for both urothelium and smooth muscle regeneration however, other types of stem cells should be more investigated for ureter tissue engineering.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 92-99"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105638","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}