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负载游离戊二醛明胶微球的间充质干细胞通过促进表达来缓解骨关节炎。

Free glutaraldehyde gelatin microsphere loaded mesenchymal stem cells alleviate osteoarthritis by promoting expression.

作者信息

Yuan Ye, Xu Longsheng, Zhao Yu, Yan Tizhen, Zhuo Baobiao, Bu Fan, Cai Qian, Xu Youjia, Bi Qing, Tong Yu, Xing Dan, Sun Di, Lin Jianhao

机构信息

Arthritis Clinic & Research Center, Peking University People's Hospital, Peking University, Beijing, 100044, China; Arthritis Institute, Peking University, Beijing 100044, China.

Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.

出版信息

Theranostics. 2025 Mar 10;15(9):4135-4146. doi: 10.7150/thno.109468. eCollection 2025.

DOI:10.7150/thno.109468
PMID:40213660
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11980673/
Abstract

Osteoarthritis (OA) is a chronic joint disorder with limited treatment efficacy, necessitating innovative therapeutic strategies. This study explores one-pot-synthesized gelatin microspheres devoid of glutaraldehyde as a novel biomaterial for OA management. Focusing on the gene, critical for cartilage development and downregulated in OA, we investigated its restoration and immune regulation using gelatin microspheres cultured with mesenchymal stem cells (MSCs). OA patients undergoing knee replacement surgery have their lateral compartment (remote zone) and medial compartment (lesion zone) cartilage collected for transcriptomic testing. The differential gene is identified, and the expression of immune regulatory genes is examined. MSCs were cultured with gelatin microspheres to evaluate their compatibility and ability to promote cell attachment. The effects of the gelatin microspheres on gene overexpression, immune regulation, and OA symptom mitigation were investigated through and experiments. OA patients exhibit decreased expression of the gene in the medial compartment (lesion zone) cartilage area, accompanied by abnormal expression of immune regulatory genes. The study demonstrated that the gelatin microspheres exhibited excellent compatibility with MSCs and facilitated their attachment. Culturing MSCs with the microspheres led to enhanced overexpression of the gene, which is crucial for cartilage growth and development. Additionally, the microspheres regulated immune responses, contributing to a reduction in OA symptoms. This study introduces an innovative therapeutic strategy for osteoarthritis using gelatin microspheres cultured with MSCs. By promoting gene overexpression and regulating immune responses, these microspheres effectively mitigate OA symptoms. The findings highlight the potential of this biomaterial as a promising treatment option for OA.

摘要

骨关节炎(OA)是一种治疗效果有限的慢性关节疾病,因此需要创新的治疗策略。本研究探索了一种无戊二醛的一锅法合成明胶微球,作为一种用于骨关节炎治疗的新型生物材料。聚焦于对软骨发育至关重要且在骨关节炎中表达下调的基因,我们研究了用间充质干细胞(MSCs)培养的明胶微球对该基因的恢复作用及其免疫调节作用。接受膝关节置换手术的骨关节炎患者的外侧间室(远端区域)和内侧间室(病变区域)软骨被收集用于转录组检测。识别差异基因,并检测免疫调节基因的表达。将间充质干细胞与明胶微球一起培养,以评估它们的相容性以及促进细胞附着的能力。通过[具体实验名称1]和[具体实验名称2]实验研究了明胶微球对该基因过表达、免疫调节和骨关节炎症状缓解的影响。骨关节炎患者在内侧间室(病变区域)软骨区域的该基因表达降低,同时伴有免疫调节基因的异常表达。研究表明,明胶微球与间充质干细胞表现出优异的相容性,并促进它们的附着。用微球培养间充质干细胞导致对软骨生长和发育至关重要的该基因的过表达增强。此外,微球调节免疫反应,有助于减轻骨关节炎症状。本研究介绍了一种使用与间充质干细胞一起培养的明胶微球治疗骨关节炎的创新治疗策略。通过促进该基因的过表达和调节免疫反应,这些微球有效地减轻了骨关节炎症状。这些发现突出了这种生物材料作为骨关节炎一种有前景的治疗选择的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/d316818767b0/thnov15p4135g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/0c1ffefa0268/thnov15p4135g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/7154edd5b33a/thnov15p4135g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/bea9274274fd/thnov15p4135g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/3bd9bc171fa3/thnov15p4135g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/ce0b13c593fe/thnov15p4135g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/d316818767b0/thnov15p4135g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/0c1ffefa0268/thnov15p4135g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/7154edd5b33a/thnov15p4135g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/bea9274274fd/thnov15p4135g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/3bd9bc171fa3/thnov15p4135g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/ce0b13c593fe/thnov15p4135g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/512e/11980673/d316818767b0/thnov15p4135g006.jpg

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本文引用的文献

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Functional biomaterials for osteoarthritis treatment: From research to application.用于骨关节炎治疗的功能性生物材料:从研究到应用。
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Injectable Bioactive Antioxidative One-Component Polycitrate Hydrogel with Anti-Inflammatory Effects for Osteoarthritis Alleviation and Cartilage Protection.可注射的生物活性抗氧化单组分聚柠檬酸盐水凝胶,具有抗炎作用,可缓解骨关节炎和保护软骨。
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Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering.利用膝关节驻留间充质干细胞进行软骨组织工程。
Acta Biomater. 2023 Sep 15;168:372-387. doi: 10.1016/j.actbio.2023.07.024. Epub 2023 Jul 21.
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3D Bioprinting Strategies for Articular Cartilage Tissue Engineering.3D 生物打印在关节软骨组织工程中的策略。
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Treatment with Mesenchymal Stem Cell-Derived Nanovesicle-Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization.基于间充质干细胞衍生纳米囊泡的明胶甲基丙烯酰水凝胶治疗通过调节软骨生成和巨噬细胞极化缓解骨关节炎。
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