Stem Cell Research & Therapy最新文献

{"title":"Correction: ZO-1 boosts the in vitro self-renewal of pre-haematopoietic stem cells from OCT4-reprogrammed human hair follicle mesenchymal stem cells through cytoskeleton remodeling.","authors":"Yingchun Ruan, Xingang Huang, Pengpeng Sun, Xiaozhen Yu, Xiaohua Tan, Yaolin Song, Hua Chen, Zhijing Liu","doi":"10.1186/s13287-025-04259-9","DOIUrl":"10.1186/s13287-025-04259-9","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"126"},"PeriodicalIF":7.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High throughput morphological screening identifies chemically defined media for mesenchymal stromal cells that enhances proliferation and supports maintenance of immunomodulatory function.","authors":"Thomas M Spoerer, Andrew M Larey, Winifred Asigri, Kanupriya R Daga, Ross A Marklein","doi":"10.1186/s13287-025-04206-8","DOIUrl":"10.1186/s13287-025-04206-8","url":null,"abstract":"<p><strong>Background: </strong>While mesenchymal stromal cell (MSC) therapies show promise for treating several indications due to their regenerative and immunomodulatory capacity, clinical translation has yet to be achieved due to a lack of robust, scalable manufacturing practices. Expansion using undefined fetal bovine serum (FBS) or human platelet lysate contributes to MSC functional heterogeneity and limits control of product quality. The need for tunable and consistent media has thus motivated development of chemically defined media (CDM). However, CDM development strategies are often limited in their screening approaches and unable to reliably assess the impact of media on MSC function, often neglecting high-level interactions of media components such as growth factors. Given that MSC morphology has been shown to predict their immunomodulatory function, we employed a high throughput screening (HTS) approach to elucidate effects of growth factor compositions on MSC phenotype and proliferation in a custom CDM.</p><p><strong>Methods: </strong>HTS of eight growth factors in a chemically defined basal medium (CDBM) was conducted via a two-level, full factorial design using adipose-derived MSCs. Media hits were identified leveraging cell counts and morphological profiles. After validating phenotypic responses to hits across multiple donors, MSCs were cultured over three passages in serum-containing medium (SCM) and CDM hits and assayed for growth and immunomodulatory function. Finally, growth factor concentrations in one hit were further refined, and MSC growth and function was assessed.</p><p><strong>Results: </strong>Our HTS approach led to the discovery of several CDM formulations that enhanced MSC proliferation and demonstrated wide ranging impacts on MSC immunomodulation. Notably, two hits showed 4X higher growth compared to SCM over 3 passages without compromising immunomodulatory function. Refinement of one CDM hit formulation reduced growth factor concentrations by as much as 90% while maintaining superior growth and similar function to SCM. Altogether, distinct MSC morphological profiles observed from screening were indicative of differential MSC quality that allowed for development of an effective CDM for MSC expansion.</p><p><strong>Conclusions: </strong>Overall, this highlights how our HTS approach led to the development of CDM formulations for robust MSC expansion and serves as a generalizable tool for improvement of MSC manufacturing processes.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"125"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Golgicide A induces pyroptosis of lung cancer stem cells by regulating dTGN formation via GOLPH3/MYO18A complex.","authors":"Feng Zhang, Sun-Han Zhang, Teng Liu, Guang-Su Xie, Shi-Hua Deng, Ting Zhang, Xiao-Bian Wang, Yue-Yan Yang, Zi-Xin Chen, Dong-Ming Wu, Ying Xu","doi":"10.1186/s13287-025-04246-0","DOIUrl":"10.1186/s13287-025-04246-0","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is a common malignant neoplasm, one of the leading causes of death worldwide. Cancer stem cells (CSCs) drive tumor recurrence, progression, and therapeutic resistance. Thus, targeting CSCs may contribute to lung cancer treatment and improve clinical outcomes.</p><p><strong>Methods: </strong>We induced stem cell formation in serum-free suspension culture. Cell viability was assessed using the cell counting-kit 8 assay, and cell membrane integrity was evaluated using the lactate dehydrogenase release assay. Caspase-1 activity assays, western blotting, enzyme-linked immunosorbent assay, and flow cytometry were used to analyze pyroptosis in cells. Confocal microscopy was used to detect protein co-localization. Quantification of fluorescence intensity and co-localization was carried out using ImageJ software. Co-immunoprecipitation was performed to assess the interaction between GOLPH3 and MYO18A. An animal study was conducted to evaluate the effects of golgicide A (GCA) on tumor growth in vivo.</p><p><strong>Results: </strong>GCA induced cell death via pyroptosis in both H1650- and A549-derived CSCs. GCA enhanced the binding of GOLPH3 and MYO18A, resulting in trans-Golgi network (TGN) dispersion. In turn, the dispersed TGN (dTGN) recruited NLRP3. Our xenograft animal model study confirmed that GCA can inhibit tumor growth.</p><p><strong>Conclusions: </strong>GCA induced pyroptosis by promoting the interaction between GOLPH3 and MYO18A, resulting in dTGN formation in lung CSCs. Our findings provide a novel molecular insight into the anti-cancer activities of GCA in lung CSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"121"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal/stem cells from perinatal sources: biological facts, molecular biomarkers, and therapeutic promises.","authors":"Mohammed Z Allouh, Syed Faizan Ali Rizvi, Ali Alamri, Yusuf Jimoh, Salma Aouda, Zakaria H Ouda, Mohammad I K Hamad, Mick Perez-Cruet, G Rasul Chaudhry","doi":"10.1186/s13287-025-04254-0","DOIUrl":"10.1186/s13287-025-04254-0","url":null,"abstract":"<p><p>The use of mesenchymal stem cells (MSCs) from perinatal tissue sources has gained attention due to their availability and lack of significant ethical or moral concerns. These cells have a higher proliferative capability than adult MSCs and less immunogenic or tumorigenesis risk than fetal and embryonic stem cells. Additionally, they do not require invasive isolation methods like fetal and adult MSCs. We reviewed the main biological and therapeutic aspects of perinatal MSCs in a three-part article. In the first part, we revised the main biological features and characteristics of MSCs and the advantages of perinatal MSCs over other types of SCs. In the second part, we provided a detailed molecular background for the main biomarkers that can be used to identify MSCs. In the final part, we appraised the therapeutic application of perinatal MSCs in four major degenerative disorders: degenerative disc disease, retinal degenerative diseases, ischemic heart disease, and neurodegenerative diseases. In conclusion, there is no single specific molecular marker to identify MSCs. We recommend using at least two positive markers of stemness (CD29, CD73, CD90, or CD105) and two negative markers (CD34, CD45, or CD14) to exclude the hematopoietic origin. Moreover, utilizing perinatal MSCs for managing degenerative diseases presents a promising therapeutic approach. This review emphasizes the significance of employing more specialized progenitor cells that originated from the perinatal MSCs. The review provides scientific evidence from the literature that applying these progenitor cells in therapeutic procedures provides a greater regenerative capacity than the original primitive MSCs. Finally, this review provides a valuable reference for researchers exploring perinatal MSCs and their therapeutic applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"127"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of mesenchymal stem cells in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.","authors":"Mumin Cao, Zhengkuan Ou, Renwang Sheng, Qianqian Wang, Xiangxu Chen, Cheng Zhang, Guangchun Dai, Hao Wang, Jiamin Li, Xihan Zhang, Yucheng Gao, Liu Shi, Yunfeng Rui","doi":"10.1186/s13287-025-04252-2","DOIUrl":"10.1186/s13287-025-04252-2","url":null,"abstract":"<p><strong>Background: </strong>The aim of this meta-analysis was to investigate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) alone for the treatment of unoperated knee osteoarthritis (OA).</p><p><strong>Methods: </strong>Four databases were systematically searched (before August 1, 2024) to include randomized controlled trials (RCTs) of MSCs for OA. The population of this study was OA patients who had not received any surgical treatment. The intervention was intra-articular injection of MSCs without other adjuvant therapy. Outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 100-mm Visual Analog Score (VAS), Knee Injury and Osteoarthritis Prognostic Score (KOOS), and adverse events. After screening the literature according to the eligibility criteria, extracting the data, and evaluating the quality, Meta-analysis was performed using Revman 5.3 software. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.</p><p><strong>Results: </strong>8 RCTs and 502 patients with OA were included in the study. Compared with the control group, MSCs significantly improved 6-month WOMAC [MD = 7.44, 95% CI = (1.45, 13.42), P = 0.01] and 12-month WOMAC [MD = 10.31, 95% CI = (0.96, 19.67), P = 0.03]. MSCs also improved VAS and KOOS at 6 and 12 months in patients with OA. Subgroup analysis showed more significant efficacy of adipose source and high doses of MSCs. There was no significant difference between the adverse events in the MSCs group and the control group (P > 0.05).</p><p><strong>Conclusion: </strong>Intra-articular injection of MSCs alone could significantly improve knee pain and dysfunction in patients with unoperated OA. MSCs are expected to be an effective treatment for OA with enhanced delivery efficiency.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"122"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human dental pulp stem cells for spinal cord injury.","authors":"Kaizhong Wang, Xiangyan Liu, Xukai Jiang, Shuang Chen, Hui Wang, Zhenbo Wang, Qiwen Wang, Zhonghai Li","doi":"10.1186/s13287-025-04244-2","DOIUrl":"10.1186/s13287-025-04244-2","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious neurological disorder that causes loss of mobility, pain, and autonomic dysfunction, resulting in altered sensation and devastating loss of function. Current treatments for SCI mainly focus on surgery and drug therapy to promote neurological recovery. However, there are virtually no effective remedies for irreversible nerve damage that result in a victim's loss of motor function and sensory changes that occur after an injury. With the continuous development of medical technology, stem-cell-based regenerative medicine provides researchers with new treatment ideas. The effectiveness of mesenchymal stem cells and their derivatives from different sources in treating SCI varies. Recent studies have highlighted that dental pulp stem cells (DPSCs) may contribute to anti-inflammatory regulation, anti-apoptotic regulation, and axonal regeneration in the treatment of SCI patients. In addition, the combination of new biomaterials and dental pulp stem cells is promising in the treatment of SCI. This article reviews the role of DPSCs in SCI treatment in recent years, discusses the advantages of DPSCs, explores potential development directions, and looks forward to providing new insights for future research in this critical field.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"123"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects and mechanisms of breastmilk stem cells in the treatment of white matter injury in newborn rats.","authors":"Meng Zhang, Haoran Wang, Yang He, Wenxing Li, Hongju Chen, Xinyu Zhang, Qiang Chen, Chao Yang, Maowen Luo, Bo Zhang, Jun Tang, Dezhi Mu","doi":"10.1186/s13287-025-04257-x","DOIUrl":"10.1186/s13287-025-04257-x","url":null,"abstract":"<p><strong>Background: </strong>Breastmilk stem cells (BSCs) have been reported to have potential benefits for infants. However, whether the BSCs could improve brain injury is unknown. A culture system for BSCs was established, and the roles of BSCs in treating white matter injury (WMI) were investigated in our study.</p><p><strong>Methods: </strong>Breastmilk samples were collected from healthy lactating women between days 1 and 5 after delivery. The BSCs were cultured in a specialized culture medium and then characterized through flow cytometry and immunofluorescence methods. A rat model with WMI was established by ligating the right carotid artery of Sprague-Dawley rats at postnatal day 3 (P3) and exposing the rats to 6% hypoxia for 2 h. Rats were categorized into sham, WMI with breastmilk cell (WMI + BC), and WMI with (WMI + NS) groups. In the WMI + BC group, 5 µL BCs (1 × 10⁶) was injected into the lateral ventricle 24 h post-modeling. Four different stages of oligodendrocyte (OL) markers were observed. Long-term neurobehavioral evaluations were conducted using the Morris water maze test. The inflammatory cytokines and proportion of proinflammatory microglial cells were detected to study the mechanisms of BSC treatment.</p><p><strong>Results: </strong>The isolated BSCs expressed mesenchymal stem cell-positive markers, including CD105, CD73, CD29, CD166, CD44, and CD90. Meanwhile, the mesenchymal stem cell-negative markers, including HLA-DR, CD45, and CD79a, were also found in BSCs. The BSCs did not express pluripotent stem cell markers, including SOX2, Nanog, OCT4, SSEA4, and TRA-1-60. Immunofluorescence detection showed that BSCs expressed neural stem/progenitor cell markers, including Vimentin, Nestin, and A2B5. Following BSC treatment, pathological improvements were observed in WMI. The expressions of mature OLs markers myelin basic protein and myelin-associated glycoprotein were increased in the corpus callosum and periventricular areas. Meanwhile, the numbers of myelin sheath increased, and learning and memory abilities improved. Furthermore, a decrease in B7-2+/Iba1 + proinflammatory microglia and an increase in CD206+/Iba1 + anti-inflammatory microglia were observed. The mRNA expressions of proinflammatory factors (Il1b, Il6, Ifng, and Tnfa) and anti-inflammatory factors (Arg1 and Tgfb) decreased and increased, respectively.</p><p><strong>Conclusion: </strong>Our findings suggest that BSCs can improve the maturation of OLs following WMI in newborn rats. The mechanisms may be attributed to the reduced proinflammatory microglia cells and factors as well as the increased anti-inflammatory microglia cells and factors.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"124"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human clinical study of an embryonic stem cell product for urea cycle disorders.","authors":"Akihiro Umezawa, Akinari Fukuda, Reiko Horikawa, Hajime Uchida, Shin Enosawa, Yoshie Oishi, Naoko Nakamura, Kengo Sasaki, Yusuke Yanagi, Seiichi Shimizu, Toshimasa Nakao, Tasuku Kodama, Seisuke Sakamoto, Itaru Hayakawa, Saeko Akiyama, Noriaki Saku, Shoko Miyata, Kenta Ite, Palaksha Kanive Javaregowda, Masashi Toyoda, Hidenori Nonaka, Kazuaki Nakamura, Yoshikazu Ito, Yasuyuki Fukuhara, Osamu Miyazaki, Shunsuke Nosaka, Kazuhiko Nakabayashi, Chizuko Haga, Takako Yoshioka, Akira Masuda, Takashi Ohkura, Mayu Yamazaki-Inoue, Masakazu Machida, Rie Abutani-Sakamoto, Shoko Miyajima, Hidenori Akutsu, Yoichi Matsubara, Takashi Igarashi, Mureo Kasahara","doi":"10.1186/s13287-025-04162-3","DOIUrl":"10.1186/s13287-025-04162-3","url":null,"abstract":"<p><strong>Background: </strong>This study assesses the safety and efficacy of hepatocyte-like cell (HLC) infusion therapy derived from human embryonic stem cells as bridging therapy for neonatal-onset urea cycle disorders (UCD). The research includes both preclinical and clinical evaluations to determine the feasibility of HLC infusion as a therapeutic option for safer pediatric liver transplantation.</p><p><strong>Methods: </strong>Preclinical studies were conducted to validate the safety, biodistribution, and ammonia metabolism capabilities of HLCs using SCID mice models of UCD and extensive animal studies. In the clinical trial, five neonates with UCD received HLC infusions, intending to maintain metabolic stability and exceed a target weight of over 6 kg, which is considered necessary for safer liver transplantation.</p><p><strong>Results: </strong>Preclinical studies demonstrated that HLCs successfully engrafted in the liver without adverse migration or tumor formation and effectively elongated survival. Clinically, all five neonates exceeded the target weight of 6 kg while maintaining metabolic stability and successfully bridging to transplantation. Post-transplantation follow-up revealed stable growth, metabolic control, and no neurological complications.</p><p><strong>Conclusions: </strong>The combined preclinical and clinical findings support HLC infusion as a viable bridge therapy for neonates with UCD, providing metabolic support to achieve safer weight thresholds for transplantation. While promising, careful monitoring remains essential, particularly for potential complications such as thrombus formation.</p><p><strong>Trial registration: </strong>jRCT, jRCT1090220412. Registered on 27 February 2019, https://jrct.niph.go.jp/en-latest-detail/jRCT1090220412 (originally registered in JMACCT (JMA-IIA00412)).</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"120"},"PeriodicalIF":7.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The local pulsatile parathyroid hormone delivery system induces the osteogenic differentiation of dental pulp mesenchymal stem cells to reconstruct mandibular defects.","authors":"Yuanyuan Jia, Mianmian Duan, Yan Yang, Duchenhui Li, Dongxiang Wang, Zhenglong Tang","doi":"10.1186/s13287-025-04258-w","DOIUrl":"10.1186/s13287-025-04258-w","url":null,"abstract":"<p><strong>Background: </strong>Tumors and injuries often lead to large mandibular defects. Accelerating the osteogenesis of large bone defect areas is a major concern in current research. In this study, dental pulp mesenchymal stem cells (DPSCs) were used as seed cells, and the local pulsatile parathyroid hormone (PTH) delivery system was used as an osteogenic-inducing active ingredient to act on DPSCs and osteoblasts, which were applied to the jaw defect area to evaluate its therapeutic effect on bone regeneration.</p><p><strong>Methods: </strong>Pulsatile delivery systems, both with and without PTH, were developed following the protocols outlined in our previous study. In vitro, the biocompatibility of the pulsatile delivery system with DPSCs was assessed using the Cell Counting Kit-8 (CCK8) assay and live/dead cell staining. Osteogenic differentiation was evaluated through alkaline phosphatase staining and alizarin red staining. In vivo, critical bone defects with a diameter of 10 mm were created in the mandibles of white rabbits. The osteogenic effect was further assessed through gross observation, X-ray imaging, and histological examination.</p><p><strong>Results: </strong>In vitro experiments using CCK8 assays and live/dead cell staining demonstrated that DPSCs successfully adhered to the surface of the PTH pulsatile delivery system, showing no significant difference compared to the control group. Furthermore, alkaline phosphatase staining and Alizarin Red staining confirmed that the localized pulsatile parathyroid hormone delivery system effectively induced the differentiation of DPSCs into osteoblasts, leading to the secretion of abundant calcium nodules. Animal studies further revealed that the PTH pulsatile delivery system promoted the osteogenic differentiation of DPSCs, facilitating the repair of critical mandibular bone defects.</p><p><strong>Conclusion: </strong>The rhythmic release of PTH from the pulsatile delivery system effectively induces the osteogenic differentiation of DPSCs. By leveraging the synergistic interaction between PTH and DPSCs, this approach facilitates the repair of extensive mandibular bone defects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"119"},"PeriodicalIF":7.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin K inhibition promotes efficient differentiation of human embryonic stem cells to mature cardiomyocytes by mediating glucolipid metabolism and cellular energy homeostasis.","authors":"Ying Wang, Yang Cui, Xiaoyu Liu, Shengxian Liang, Li Zhong, Rui Guo","doi":"10.1186/s13287-025-04231-7","DOIUrl":"10.1186/s13287-025-04231-7","url":null,"abstract":"<p><strong>Background and aim: </strong>Generation of functional cardiomyocytes from human pluripotent stem cells (hPSCs) offers promising applications for cardiac regenerative medicine. Proper control of pluripotency and differentiation is vital for generating high-quality cardiomyocytes and repairing damaged myocardium. Cathepsin K, a lysosomal cysteine protease, is a potential target for cardiovascular disease treatment; however, its role in cardiomyocyte differentiation and regeneration is unclear. This study aims to investigate the effects and mechanisms of cathepsin K inhibition on the differentiation of human embryonic stem cell-induced cardiomyocytes (hESC-CMs) and myocardial generation.</p><p><strong>Methods: </strong>We cultured H9-hESCs in CDM3 medium to induce myocardial differentiation, adding cathepsin K inhibitor II (1 μM) on days 2, 5 and 8, respectively. Cells were observed and collected 48 h after each treatment. The morphology and contractile clusters of H9-hESCs were tracked with microscopy and video recording. Pluripotency and cardiac markers were assessed at each stage of differentiation. We also examined glucose and lipid metabolism, mitochondrion-related markers, apoptosis and autophagy.</p><p><strong>Results: </strong>CDM3 medium effectively differentiated high-density H9-hESCs into mature, spontaneously contracting cardiomyocytes. Cathepsin K inhibition accelerates the differentiation of H9-hESCs into cardiac mesoderm and cardiac precursor cells (CPCs) by reducing apoptosis, decreasing glycolysis and fatty acid metabolism at the early and middle stages, and subsequently facilitate the development and differentiation of cardiomyocytes by enhancing glucolipid metabolism and oxidative phosphorylation at the late stage. Meanwhile, cathepsin K inhibition enhanced mitochondrial function and lysosome-related gene transcription during the differentiation process.</p><p><strong>Conclusion: </strong>Our study highlights the potential of cathepsin K inhibition for renewable cardiomyocytes and suggests exploring metabolic pathways and signaling to improve cardiac regeneration and organoid development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"118"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}