Tissue engineering and regenerative medicine最新文献

{"title":"Establishment of Immune-Evasive iPSCs from PBMCs Using B2M Knockout and CD47/HLA-E Overexpression.","authors":"Cha Yeon Kim, Cholong Jeong, Yeon-Ju Jeong, Young Hoon Sung, Youngjin Han, Changmo Hwang","doi":"10.1007/s13770-025-00742-9","DOIUrl":"https://doi.org/10.1007/s13770-025-00742-9","url":null,"abstract":"<p><strong>Background: </strong>Induced pluripotent stem cells (iPSCs) represent a promising source for regenerative therapies, yet allogeneic transplantation is limited by immune rejection. While strategies for generating hypoimmune iPSCs have been proposed, their efficacy after differentiation into lineage-specific cell types remains underexplored.</p><p><strong>Methods: </strong>A human iPSC line (36A) from peripheral blood mononuclear cells using a Sendai virus-based reprogramming protocol. Hypoimmune properties were conferred via CRISPR-Cpf1-mediated B2M knockout, combined with lentiviral overexpression of HLA-E and CD47. Immune evasion was validated using NK cell cytotoxicity assays. Endothelial differentiation was induced using a defined, stepwise protocol, and in vivo functionality was evaluated in humanized NSG mice.</p><p><strong>Results: </strong>The hypoimmune iPSCs retained pluripotency, exhibited stable karyotype, and demonstrated > 99% expression of HLA-E/CD47. NK cell-mediated lysis was significantly reduced in edited cells, although IFN-γ levels remained elevated. Upon differentiation, the hypoimmune iPSCs yielded > 98% CD31⁺CD144⁺ endothelial cells, which showed enhanced survival in vivo compared to wild-type controls.</p><p><strong>Conclusion: </strong>Multiplex gene editing successfully conferred durable immune evasion in both undifferentiated and endothelial-differentiated iPSCs. These findings support the clinical potential of hypoimmune iPSC-derived cell therapies for allogeneic transplantation without immunosuppression.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circRNA_Atp8a1 Promotes Glycolytic Reprogramming in Damage of Intestinal Mucosal Barrier by Upregulating IGF2 through miR-200b-3p.","authors":"Wen Qiang Yuan, Yun Han Yang, Peng Shuang Shi, Shi Min Wu, Fang Yan, De Jun Cui","doi":"10.1007/s13770-025-00737-6","DOIUrl":"https://doi.org/10.1007/s13770-025-00737-6","url":null,"abstract":"<p><strong>Background: </strong>This study investigated a circRNA (Circ_Atp8a1) in regulating intestinal epithelial repair in intestinal mucosal barrier damage.</p><p><strong>Methods: </strong>A mouse model of intestinal mucosal barrier damage caused by burn injury was constructed. Skin and intestinal histopathologic changes in injured and control mice were compared. Glycolytic enzyme protein expression, lactate production, and glucose consumption in intestinal tissues were detected. Microarray analysis was used to screen differentially expressed circRNAs in mucosal tissues, and RT-qPCR, Sanger sequencing, RNAse R test, nucleoplasmic isolation experiments, and fluorescence in situ hybridization (FISH) were used to characterize the circular structure and localization of Circ_Atp8a1. In Caco-2 cells, adenoviral overexpression vector and small interfering RNA (siRNA) were constructed to regulate Circ_Atp8a1 expression. Cell proliferation and migration were detected by combining with the experiments of CCK-8, EdU, wound healing, and Transwell. The interaction between Circ_Atp8a1 and miR-200b-3p was investigated by dual luciferase reporter assay, RNA pull-down assay, and FISH assay. The target gene of miR-200b-3p was predicted and validated. Finally, the effects of intraperitoneal injection of KD-Circ_Atp8a1 and OE-Circ_Atp8a1 on intestinal mucosal damage in burned mice were observed by in vivo experiments.</p><p><strong>Results: </strong>Mice with burn-induced intestinal mucosal damage had higher CMDI scores, increased expression of glycolytic enzymes in intestinal tissues, and altered glycolytic processes. A total of 308 aberrantly expressed circRNAs were screened, among which Circ_Atp8a1 was significantly down-regulated and mainly distributed in cytoplasm and jejunal crypts. In Caco-2 cells, overexpression of Circ_Atp8a1 inhibited cell proliferation, migration, and glycolysis, and knockdown of Circ_Atp8a1 did the opposite. Circ_Atp8a1 acted as a sponge for miR-200b-3p, which targeted and inhibited IGF2, which affected glycolysis-related metrics. Circ_Atp8a1 regulated IGF2 indirectly through miR-200b-3p, which in turn regulated intestinal mucosal damage. in vivo experiments showed that overexpression of Circ_Atp8a1 could inhibit miR-200b-3p expression, promote IGF2 expression, reduce intestinal mucosal damage and decrease mucosal permeability.</p><p><strong>Conclusion: </strong>Circ_Atp8a1 plays a key regulatory role in the process of intestinal mucosal damage and affects the process of glycolysis through adsorption of miR-200b-3p to regulate IGF2. It is expected to be a new target for the treatment of intestinal mucosal damage.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Construction of Chitosan Oligosaccharide-Coated Nanostructured Lipid Carriers for the Sustained Release of Strontium Ranelate.","authors":"Hayeon Lim, Yoseph Seo, Sung Jun Min, Daehyeon Yoo, Dong Nyoung Heo, Il Keun Kwon, Taek Lee","doi":"10.1007/s13770-025-00743-8","DOIUrl":"https://doi.org/10.1007/s13770-025-00743-8","url":null,"abstract":"","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strontium-Doped Marine Collagen Membranes Promote Osteogenesis by Inducing M2 Macrophage Polarization.","authors":"Hao Xu, Xin Li, Wenxue Wang, Li Zhen, Baodong Zhao","doi":"10.1007/s13770-025-00732-x","DOIUrl":"https://doi.org/10.1007/s13770-025-00732-x","url":null,"abstract":"<p><strong>Background: </strong>The design of bone biomaterials has shifted from promoting bone differentiation to \"immune osteogenic coupling\". Macrophages play a key role in immune regulation, with their polarization state critically shaping the bone tissue immune microenvironment. While collagen membranes, as classic guided bone regeneration (GBR) barriers, offer excellent biocompatibility and degradability, they lack inherent bone induction and immune regulation capabilities, limiting their use in complex bone defect repair.</p><p><strong>Methods: </strong>In this study, we proposed a novel optimization strategy utilizing phase-transited lysozymes (PTL) incorporating strontium (Sr²⁺) into marine collagen membranes (Sr-PTL-MCM) and investigate their osteoimmunomodulatory effect through a series of experiments.</p><p><strong>Results: </strong>Sr-PTL-MCM were successfully synthesized via the PTL technique and continuously released Sr²⁺ ions over 7 days. Sr-PTL-MCM can effectively induce macrophage polarization from the M0 to M2 phenotype, suppresses the secretion of inflammatory cytokines, thereby enhancing mBMSCs osteogenic differentiation. RNA-sequence analysis reveals that Sr-PTL-MCM promotes M2 polarization via JAK-STAT and MAPK signaling pathways. In vivo experiments confirm its ability to create a favorable bone immune microenvironment, promoting bone growth and regeneration.</p><p><strong>Conclusion: </strong>In conclusion, incorporating Sr ions into collagen via PTL technique represents a promising approach for developing collagen membranes with immunomodulatory characteristics, thereby providing a novel and effective strategy for bone defect repair.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Long-Term Survival and Self-Renewal of Primary Hepatocytes via Rapid Spheroid Formation Using Rocker System through Co-Culturing with HUVEC Over-Expressing RSPO1.","authors":"Yuting He, Qin Liu, Yanyan Zhou, Ji Bao","doi":"10.1007/s13770-025-00736-7","DOIUrl":"https://doi.org/10.1007/s13770-025-00736-7","url":null,"abstract":"<p><strong>Background: </strong>Porcine primary hepatocytes are vital for liver therapy due to their procurement ease and robust functions. However, they rapidly dedifferentiate in vitro, challenging large-scale maintenance. This study aims to enhance the long-term survival and self-renewal of primary porcine hepatocytes by generating spheroids using a rocker system and optimizing conditions with HUVECs and Roof plate-specific spondin 1 (RSPO1).</p><p><strong>Methods: </strong>Primary hepatocytes were co-cultured with HUVECs in a rocker system using serum-free medium to form spheroids, mimicking their native microenvironment. RSPO1 was added to the media to promote hepatocyte signaling and proliferation. Then pheroids were generated with HUVECs overexpressing RSPO1 (R-HUVECs). The effects of these conditions on the viability, hepatic function, and proliferation of hepatocytes were evaluated.</p><p><strong>Results: </strong>The 3D environment and RSPO1 synergistically enhanced hepatocyte proliferation and maintained essential liver functions long-term. Co-culture with HUVECs and R-HUVECs promoted spheroid formation, with spheroids surviving and functioning for 28 days.</p><p><strong>Conclusion: </strong>Large-scale cultured hepatocyte + R-HUVEC spheroids address in vitro challenges of scale, yield, and functional sustainability, promising advances in liver therapeutics and drug development.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT4 Regulated by a Mechanosensor, PIEZO1 Shows a Protective Function to Suppress Ox-LDL Uptake in Endothelial Cells.","authors":"Vadym Kopych, Avelino Dos Santos Da Costa, Kwideok Park","doi":"10.1007/s13770-025-00733-w","DOIUrl":"https://doi.org/10.1007/s13770-025-00733-w","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cells (ECs) are key regulators of vascular function, adapting to mechanical forces, such as shear stress to maintain vascular homeostasis. Disruption of this adaptation, particularly in the regions of disturbed flow, contributes to endothelial dysfunction and the development of atherosclerosis later on.</p><p><strong>Methods: </strong>We prepared a custom-designed PDMS-based flow chamber to apply controlled shear stress (2 or 7 dynes/cm²) to human umbilical vein endothelial cells. ECs were cultured on gelatin-coated coverslips and exposed to different shear flows for up to 12 h. Cell alignment was confirmed by angle measurements using ImageJ. Gene expression of SIRT4, PIEZO1, NOTCH1, and LOX-1 was determined via qPCR, and protein levels were assessed by western blot. Specific gene knockdown was also conducted using siRNAs, targeting either PIEZO1 or SIRT4. Oxidized LDL uptake was evaluated using DiI-labeled Ox-LDL and quantified by fluorescence imaging. Immunofluorescence staining of ECs was performed to visualize VE-cadherin, F-actin, and nuclei. All quantitative data were subjected to statistical analysis.</p><p><strong>Results: </strong>We demonstrated that the mechanosensitive ion channel PIEZO1, regulates SIRT4 expression in response to shear stress. Under atheroprotective shear stress (7 dyne/cm²), PIEZO1-mediated upregulation of SIRT4 was observed, while atheroprone shear stress (2 dyne/cm²) led to reduced expression. Functional assays showed that SIRT4 protects endothelial cells from Ox-LDL uptake, a key factor in atherosclerosis. SIRT4 silencing increased Ox-LDL accumulation even under protective flow. This effect, and its link to LOX-1, was dependent on PIEZO1 signaling.</p><p><strong>Conclusion: </strong>Current findings suggest that the PIEZO1-SIRT4 axis may modulate endothelial responses to shear stress, offering a protective mechanism against Ox-LDL-induced dysfunction and pathology. Our study underscores the potential of SIRT4 as a therapeutic target to mitigate vascular disorders associated with oxidative stress and disturbed blood flow.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short- and Medium-Term Surgical Outcomes of Tissue-Engineered Pulmonary Valve Replacement in Sheep.","authors":"Hussam Al Hussein, Hamida Al Hussein, Horatiu Suciu, David Emanuel Anitei, Carmen Sircuta, Ionela Cotfas, Bogdan Cordos, Cynthia Lefter, Klara Brinzaniuc, Dan Simionescu, Marius Mihai Harpa","doi":"10.1007/s13770-025-00735-8","DOIUrl":"https://doi.org/10.1007/s13770-025-00735-8","url":null,"abstract":"<p><strong>Background: </strong>Tissue-engineered pulmonary valves (TEPVs) hold considerable potential for improving outcomes in valve replacement surgeries. We investigated the surgical outcomes of TEPVs replacement in sheep, specifically examining the effects of valve type (decellularized versus adipose-derived stem cell-seeded valve [ADSC]) and the animal's age at the surgery. The primary goals were to assess survival rates, postoperative complications, and the effects of cardiopulmonary bypass (CPB) on homeostasis.</p><p><strong>Methods: </strong>Nineteen juvenile and adult sheep were randomly assigned to orthotopic pulmonary valve replacement using either decellularized (DECELL, n = 10) or ADSC-seeded valves (CELL, n = 9). Blood gas analysis was conducted intraoperatively and postoperatively to assess CPB-related metabolic changes. The follow-up period after surgery was 6 months. Key demographic and operative parameters were recorded, and early and late postoperative complications were monitored.</p><p><strong>Results: </strong>No significant differences were observed in operative parameters or postoperative complications between the DECELL and CELL groups. Adult sheep exhibited longer anesthesia, CPB, and operative times due to tissue fragility but demonstrated better long-term survival than juveniles, who experienced more late-stage complications, including endocarditis. CPB exposure increased lactate and reduced hemoglobin levels, particularly in adult sheep, affecting homeostasis. The overall mortality rate was 42.1%, with deaths primarily attributed to congestive heart failure and endocarditis.</p><p><strong>Conclusion: </strong>Valve type did not significantly affect short-term outcomes and ADSC-seeding had no significant impact on operative parameters, postoperative complications, or survival rate. However, age remained a crucial factor influencing both surgical complexity and survival, highlighting the need for age-specific strategies in tissue-engineered valve applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Production of 3D Neuronal Lineage Population by Morphological Classification.","authors":"Ji-Hee Choi, Yun-Gwi Park, Jongil Ju, Soon-Jung Park, Sung-Hwan Moon","doi":"10.1007/s13770-025-00721-0","DOIUrl":"10.1007/s13770-025-00721-0","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of neurodegenerative diseases and toxic substance exposure highlights the need for neuronal cell models that closely mimic human neurons in vivo. Compared to traditional models, human pluripotent stem cell (hPSC)-derived three-dimensional models mimic human physiological characteristics and complex nervous system interactions. These models enable patient-specific treatments and improve the predictive accuracy of drug toxicity evaluations. However, differentiation efficiency varies based on organoid size, structure, and cell line characteristics, necessitating standardized protocols for consistent outcome.</p><p><strong>Methods: </strong>The morphological characteristics of hPSC-derived embryonic bodies (EBs) formed by concave microwells were analyzed at the early stage of neuronal differentiation. Criteria were established to identify cells with high differentiation efficiency, enabling the optimization of differentiation methods applicable across various cell lines. Neuronal organoids were generated using a microfluidic-concave chip, and their suitability for drug toxicity testing was assessed.</p><p><strong>Results: </strong>EBs, formed in 500 µm concave microwells, exhibited the highest efficiency for neuronal cell differentiation. Cavity-like EBs were more suitable for neuronal differentiation and maturation than cystic-like forms. The optimal neuronal lineage differentiation method was established, and the drug toxicity sensitivity of organoids generated from this method was validated.</p><p><strong>Conclusions: </strong>This study identified EB structures suitable for neuronal lineage differentiation based on morphological classification. Furthermore, this study suggested an optimal method for generating neuronal organoids. This method can be applied to various cell lines, enabling its precise use in patient-specific treatments and drug toxicity tests.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"661-674"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Efficient Organoid Cutting Method for Long-Term Culture and High-Throughput Analyses.","authors":"Nicholas A Chartrain, Marina V Pryzhkova, Juliana I Candelaria, Kristin H Gilchrist, Philip W Jordan","doi":"10.1007/s13770-025-00731-y","DOIUrl":"10.1007/s13770-025-00731-y","url":null,"abstract":"<p><strong>Background: </strong>Human organoid models are invaluable for developmental studies, disease modeling, and personalized medicine research. However, long-term maintenance is challenging due to hypoxia and nutrient limitations as organoids grow. Cutting organoids improves viability, but current methods have low throughput and are prone to causing culture contamination. This study introduces an efficient organoid cutting method to enhance long-term culture and enable high-throughput analyses.</p><p><strong>Methods: </strong>We employed three-dimensional (3D) printing to fabricate four classes of organoid cutting jigs with blade guides that were compared and optimized for consistent sectioning of human pluripotent stem cell (hPSC)-derived organoids. Organoids were cultured in mini-spin bioreactors and cut every three weeks, beginning on day 35. Organoid health and growth were evaluated by size increase and proliferative marker expression. Additionally, we utilized 3D printed molds to create GelMA or Geltrex-embedded organoid arrays and silicone molds for optimal cutting temperature compound (OCT)-embedding of organoid arrays.</p><p><strong>Results: </strong>All 3D printed jigs enabled rapid and uniform organoid cutting under sterile conditions. We determined that a flat-bottom cutting jig design had superior cutting efficiency. Cutting improved nutrient diffusion, increased cell proliferation, and enhanced organoid growth during long-term culture. The mold-based approaches enabled the creation of densely packed organoid arrays and cryosections with evenly distributed organoids.</p><p><strong>Conclusion: </strong>This novel organoid cutting and arraying method overcomes limitations in long-term organoid culture and high-throughput processing. The simplicity of the cutter design and handling make it a versatile tool for diverse types of organoids. By enhancing organoid viability and enabling consistent sample preparation, this approach facilitates improved organ development and disease modeling, drug screening, and high-throughput analyses, including single-cell spatial transcriptomics applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"675-690"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTH Promotes Chondrogenesis of Fibrocartilage Stem Cells and Alleviates Temporomandibular Joint Osteoarthritis.","authors":"Zhihang Yue, Wuyi Gong, Haojun Chu, Yongming Li","doi":"10.1007/s13770-025-00723-y","DOIUrl":"10.1007/s13770-025-00723-y","url":null,"abstract":"<p><strong>Background: </strong>Parathyroid hormone (PTH) can promote subchondral bone formation and alleviate temporomandibular joint (TMJ) osteoarthritis (OA), but the effects of PTH on fibrocartilage stem cells (FCSCs) in cartilage surfaces have yet to be studied.</p><p><strong>Methods: </strong>We established the TMJOA model in rats and administered PTH to treat them. Rat condyles were analyzed using micro-computed tomography, histological, and immunohistochemical staining. To study PTH's effects on FCSCs in vitro, we employed quantitative polymerase chain reaction, Western Blot, and immunofluorescence staining. We also constructed the TMJOA model in tdTomato; Cathepsin K (Ctsk)-Cre mice and rescued them with PTH. EdU and immunofluorescence staining were used to measure the proliferation and chondrogenic differentiation of FCSCs in vivo. Furthermore, after discectomy, we injected diphtheria toxin (DT) into the Ctsk-Cre; diphtheria toxin receptor (DTR) mice to ablate FCSCs. Afterwards, PTH was injected, and we evaluated the Collagen Type II Alpha 1 (COL2A1)-positive area using immunofluorescence staining.</p><p><strong>Results: </strong>We successfully developed a TMJOA model, and after treatment with PTH, the rat condyles' BV/TV and Tb. Th increased, and the expression of chondrogenic-related genes was elevated. Additionally, PTH promoted the chondrogenic differentiation of FCSCs in vitro. In tdTomato; Ctsk-Cre mice, the Ctsk/EdU and Ctsk/COL2A1 double-positive cells were increased after PTH administration. Moreover, after the ablation of FCSCs by DT, the effects of PTH treatment were notably reduced.</p><p><strong>Conclusion: </strong>PTH promotes the proliferation and chondrogenic differentiation of condylar FCSCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"705-718"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}