Regenerative Therapy最新文献

{"title":"Standardizing decellularization protocols for optimized uterine tissue bioengineering","authors":"Edina Sehic ,&nbsp;Lucía de Miguel-Gómez","doi":"10.1016/j.reth.2024.12.011","DOIUrl":"10.1016/j.reth.2024.12.011","url":null,"abstract":"<div><div>Bioengineering is applied in different areas, including women's infertility management. Among other approaches, decellularized tissues are being used to treat uterine disorders causing infertility. Biomaterials made from decellularized tissue consist of tissue-specific extracellular matrix and, as acellular scaffolds, are thought to be immune inert. Hence, they are good grafting candidates to replace and regenerate excised damaged uterine tissue to cure infertility. However, decellularization approaches differ among species and research groups, posing challenges for comparison and standardization. The diversity in data reporting and studied properties of the resulting decellularized scaffold make it even more difficult, especially when the ultimate goal is clinical translation. Thus, this review aims to critically assess whole uterus decellularization studies, extracting and comparing their main results and conclusions. After carefully evaluating the reviewed studies, we noticed that the vast majority base the uterus decellularization success and resulting scaffold efficacy on the DNA removal efficacy, while other crucial aspects, including the extracellular matrix integrity or immunogenicity, are underestimated. Thus, this review further proposes practical points for what should be considered and how results can be reported in studies involving whole uterus decellularization to facilitate comparison between studies and translational progress.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 183-190"},"PeriodicalIF":3.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-Quercetin complex enhances mesenchymal stem cell-mediated HGF secretion and c-Met activation to ameliorate acute kidney injury through the prevention of tubular cell apoptosis","authors":"Yuan-Xia Zou ,&nbsp;Jiraporn Kantapan ,&nbsp;Hong-Lian Wang ,&nbsp;Jian-Chun Li ,&nbsp;Hong-Wei Su ,&nbsp;Jian Dai ,&nbsp;Nathupakorn Dechsupa ,&nbsp;Li Wang","doi":"10.1016/j.reth.2024.12.003","DOIUrl":"10.1016/j.reth.2024.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSC^IronQ). Renal function, histology, and tubular cell apoptosis were analyzed three days post-treatment. In vitro, apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSC^IronQ conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA sequencing (RNA-seq) was performed on MSC^IronQ to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>Compared to MSC-treated AKI mice, those treated with MSC^IronQ showed significantly improved renal function and histological outcomes, with reduced tubular cell apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSC^IronQ-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSC^IronQ on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models.</div></div><div><h3>Conclusions</h3><div>IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 169-182"},"PeriodicalIF":3.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of SFRP1 in human dermal papilla cell growth and its potential molecular mechanisms as a target in regenerative therapy","authors":"Chaofan Wang ,&nbsp;Yimei Du ,&nbsp;Changpei Lu ,&nbsp;Lingbo Bi ,&nbsp;Yunbu Ding ,&nbsp;Weixin Fan","doi":"10.1016/j.reth.2024.12.001","DOIUrl":"10.1016/j.reth.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla. TERT levels can be enhanced by activation of the Wnt pathway in cancer cells and embryonic stem cells. Whether this regulatory mechanism is still present in DPCs has not been studied so far.</div></div><div><h3>Methods</h3><div>In this study, DNA plasmids and siRNAs were constructed against the SFRP1 gene and transfected into DPCs cultured in vitro. We detected the viability, proliferation, and migration of DPCs by Calcein/PI fluorescence, CCK-8, <em>trans</em>-well, or cell scratch experiments, and the expression of potential target genes was also determined through quantitative detection of RNA and protein.</div></div><div><h3>Results</h3><div>The results demonstrate a significant difference in SFRP1 levels from the control group, suggesting successful transfection of the DNA plasmid and siRNA of SFRP1 into IDPCs. Also, SFRP1 regulates the cell proliferation capacity of IDPCs and reduces their migration functions. The DPCs' living activity, proliferation, and migration function exhibited a negative correlation with the level of SFRP1. SFPR1 also inhibits the protein or RNA expression of β-catenin and TERT in DPCs.</div></div><div><h3>Conclusion</h3><div>It was proven that in human DPCs, different levels of SFRP1 change how cells work and control Wnt/β-catenin signaling or telomerase activity. This means that blocking SFRP1 could become a new way to treat hair loss diseases in the future.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 161-168"},"PeriodicalIF":3.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineering strategies for regeneration of skin integrity: A literature review","authors":"Makoto Shiraishi ,&nbsp;Yoshihiro Sowa ,&nbsp;Ataru Sunaga ,&nbsp;Kenta Yamamoto ,&nbsp;Mutsumi Okazaki","doi":"10.1016/j.reth.2024.12.006","DOIUrl":"10.1016/j.reth.2024.12.006","url":null,"abstract":"<div><h3>Objective</h3><div>The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration.</div></div><div><h3>Methods</h3><div>A literature search was carried out in PubMed using combinations of the keywords “skin integrity”, “tissue-engineered skin”, “bioengineered skin”, and “skin regeneration”. Articles published from 1968 to 2023 reporting evidence from <em>in vivo</em> and <em>in vitro</em> skin regeneration experiments were included.</div></div><div><h3>Results</h3><div>These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface.</div></div><div><h3>Conclusion</h3><div>Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 153-160"},"PeriodicalIF":3.4,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIEZO1 activation enhances myogenesis and mitigates muscle degeneration in rotator cuff tear","authors":"Tihui Wang ,&nbsp;Shujing Feng ,&nbsp;Hao Zhou ,&nbsp;Wenhua Mao ,&nbsp;Ruijun Bai ,&nbsp;Yuan Xia ,&nbsp;Jianghu Huang ,&nbsp;Rui Zhang ,&nbsp;Feiyue Lin","doi":"10.1016/j.reth.2024.12.002","DOIUrl":"10.1016/j.reth.2024.12.002","url":null,"abstract":"<div><div>Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 143-152"},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NFATC2/Nrf2 cascade regulates spinal cord ischemia-reperfusion injury by controlling inflammation, apoptosis and oxidative stress","authors":"Kunbin Li ,&nbsp;Liming Lu ,&nbsp;Xianli Yao ,&nbsp;Zhiyuan Wu ,&nbsp;Pingge Sun ,&nbsp;Xiaopeng Wen ,&nbsp;Xiaoxing Li ,&nbsp;Kai Wang ,&nbsp;Xiran Yin","doi":"10.1016/j.reth.2024.11.014","DOIUrl":"10.1016/j.reth.2024.11.014","url":null,"abstract":"<div><div>Spinal cord ischemia/reperfusion (IR) injury (SCII) can cause major autonomic, sensory, and motor damage and loss. The upregulation of Nrf2, a primary orchestrator of the oxidative stress response, has beneficial effects in SCII. Here, we aimed to uncover a SCII-related transcription factor that is able to elevate Nrf2 expression. Rat PC12 cells were subjected to treatment with oxygen-glucose deprivation/reoxygenation (OGD/R) to induce an <em>in vitro</em> neuronal IR injury model. A rat model of SCII was established by blocking the left common carotid artery and aortic arch in SD rats. Cell viability and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. IL-1β and TNF-α levels were detected by ELISA. The oxidative stress was tested by assessing ROS and MDA contents and SOD and GSH-Px activity. The NFATC2/Nrf2 relationship was predicted by bioinformatic analysis and validated by ChIP and luciferase reporter assays. Nrf2 and NFATC2 levels were reduced in PC12 cells after OGD/R treatment. Nrf2 increase significantly attenuated OGD/R-triggered inflammation, apoptosis and oxidative stress in PC12 cells. Moreover, Nrf2 increase alleviated spinal cord pathological changes, inflammation, apoptosis and oxidative stress in rats after SCII. Mechanistically, NFATC2 could activate Nrf2 transcription and promote its expression. Nrf2 reduction exerted a counteracting impact on NFATC2's anti-inflammation, anti-apoptosis and anti-oxidative stress functions in PC12 cells under OGD/R conditions. Our study demonstrates that the NFATC2/Nrf2 cascade has a regulatory capacity in inflammation, apoptosis and oxidative stress after SCII.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 126-133"},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembling peptide nanofibers and nanoceramics in a model of alveolar bone repair: Insights from in vivo experiments and clinical trial","authors":"Elahe Tahmasebi ,&nbsp;Sareh Azadi ,&nbsp;Samira Hajisadeghi ,&nbsp;Hamidreza Barikani ,&nbsp;Masoud Salehi ,&nbsp;Mahdi Shafikhani ,&nbsp;Fateme Mozaffari ,&nbsp;Edris Nazarpour ,&nbsp;Arman Torabizadeh ,&nbsp;Ahad Khoshzaban","doi":"10.1016/j.reth.2024.11.011","DOIUrl":"10.1016/j.reth.2024.11.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Tooth extraction initiates a cascade of homeostatic and structural modifications within the periodontal tissues, culminating in alveolar ridge resorption. To prevent ridge resorption following extraction and facilitate successful placement of an implant-supported prosthesis, alveolar ridge preservation was performed.</div></div><div><h3>Methods</h3><div>In this study, the biocompatibility of a nanocomposite consisting of self-assembling peptide nanofibers (organic phase) and tri-calcium phosphate-nano hydroxyapatite (mineral phase), was evaluated in rabbits. Subsequently, the nanocomposite was grafted onto a model of alveolar bone repair in patients.</div></div><div><h3>Results</h3><div>The in vivo findings revealed no significant differences in the irritation ranking score and average thickness of the reaction zone between the nanocomposite and control groups. Furthermore, there were no significant differences in the appearance of necrosis, granulation tissue, fibroplasia, neovascularization, and hemorrhage as well as in the number of neutrophils, mast cells, lymphocytes, macrophages, and giant cells between the two groups. The defect area was completely filled with newly formed bone trabeculae and cavities containing bone marrow, indicating angiogenesis, while remnants of the scaffold were observed in the deeper region of the defects, adjacent to the bone marrow, considered osteoinductive. The clinical trial findings (TRN: IR.IUMS.REC.1401.355) demonstrated robust bone regeneration after 3.5 months of socket preservation, whereas the bone in the control group experienced atrophy. The nanocomposite facilitated soft tissue healing without any signs of infection or other periodontal malfunction.</div></div><div><h3>Conclusion</h3><div>The application of nanotechnology has enhanced the bio-functionality of alloplastic materials, positioning this nanocomposite a promising alternative to autografts and allografts in alveolar bone repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 134-142"},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization and therapeutic potential of human umbilical cord blood mononuclear cells","authors":"Yu Zhang ,&nbsp;Yueda Lu ,&nbsp;Xinyue Hu ,&nbsp;Mengxing Jiang ,&nbsp;Zhixiu Chen ,&nbsp;Lingkun Jin ,&nbsp;Min Li ,&nbsp;Chen Chen ,&nbsp;Jianye Wang","doi":"10.1016/j.reth.2024.11.019","DOIUrl":"10.1016/j.reth.2024.11.019","url":null,"abstract":"<div><div>Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a population of cells derived from neonatal cord blood, encompassing various stem cells and immune cells. The unique characteristics of hUCB-MNCs endow them with distinctive multifunctionality, including the promotion of angiogenesis, acceleration of tissue repair, regulation of immune responses, neuroprotection, alleviation of inflammatory reactions, enhancement of antioxidant capacity, reduction of fibrosis processes, and inhibition of apoptosis. These diverse biological properties underscore the significant clinical therapeutic potential of hUCB-MNCs, which are widely applied in the treatment of various diseases. This review aims to summarize the underlying mechanisms responsible for the multifunctional attributes of hUCB-MNCs, elucidating their potential modes of action in disease management and providing novel theoretical insights and practical guidance for their expanded application across different disease domains. By synthesizing current research findings, this review may provide insights into the potential clinical applications of hUCB-MNCs in the fields of regenerative medicine and cell therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 101-114"},"PeriodicalIF":3.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dermal white adipose tissue: A new modulator in wound healing and regeneration","authors":"Zhongyu Wu ,&nbsp;Zhanqi Wang ,&nbsp;Tao Chen ,&nbsp;Dongyang Wang ,&nbsp;Feng Zhou ,&nbsp;Guorui Zhang ,&nbsp;Shan Wei ,&nbsp;Yingying Wu","doi":"10.1016/j.reth.2024.11.015","DOIUrl":"10.1016/j.reth.2024.11.015","url":null,"abstract":"<div><div>Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging. This review highlights the regulatory potential of dWAT in modulating wound healing processes and presents it as a target for developing therapeutic strategies aimed at reducing scarring and enhancing regenerative outcomes in skin-related disorders.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 115-125"},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling vascular dynamics at the initial stage of endochondral ossification on a microfluidic chip using a human embryonic-stem-cell-derived organoid","authors":"Abhiraj Kesharwani ,&nbsp;Shoichiro Tani ,&nbsp;Masaki Nishikawa ,&nbsp;Yasuyuki Sakai ,&nbsp;Hiroyuki Okada ,&nbsp;Shinsuke Ohba ,&nbsp;Ung-il Chung ,&nbsp;Hironori Hojo","doi":"10.1016/j.reth.2024.11.018","DOIUrl":"10.1016/j.reth.2024.11.018","url":null,"abstract":"<div><div>Vascular interactions play a crucial role in embryogenesis, including skeletal development. During endochondral ossification, vascular networks are formed as mesenchymal cells condense and later invade skeletal elements to form the bone marrow. We and other groups developed a model of endochondral ossification by implanting human embryonic stem cell (hESC)-derived sclerotome into immunodeficient mice. However, <em>in vitro</em> models of endochondral ossification, particularly vascular interaction with mesenchymal cells at its initial stage, are yet to be established. Therefore, we developed a method to model the initial stage of endochondral ossification using a microfluidic chip-based platform, with a particular focus on the vascular interaction. On the chip, we found that the fibrin gel helped align mCherry-expressing human umbilical vein endothelial cells (HUVECs) better than the collagen-I gel, suggesting that the fibrin gel is more suitable for the formation of a vascular-like network. The perfusability of the vascular-like networks was partially confirmed using fluorescein isothiocyanate (FITC)-dextran and fluorescent microbeads. We then mixed hESC-derived sclerotome with enhanced green fluorescent protein (EGFP)-expressing HUVECs and applied this mixture on the chip. We named this mixture of cells SH organoids. The SH organoids showed superior abilities to maintain the vascular-like network, which was formed by the mCherry-expressing HUVECs, compared with the sclerotome spheroids on the chip. The EGFP-expressing HUVECs migrated from the SH organoid, formed a vascular-like networks, and partially interacted with the mCherry-expressing vascular-like networks on the chip. Histological analysis showed that SRY-box transcription factor 9 (SOX9) and type I collagen were expressed mutually exclusively in the condensed mesenchymal cells and perichondrial-like cells, respectively. This study demonstrates that our SH organoid-on-a-chip method reproduces vascular networks that are formed at the initial stage of endochondral ossification. This model may provide insights into human endochondral ossification and has potential applications in bone disease modeling and drug screening.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 90-100"},"PeriodicalIF":3.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}