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卡托苷元增强 3D 共聚三聚物支架和自行设计的生物反应器系统中 MSC 的软骨分化。

Kartogenin Enhances Chondrogenic Differentiation of MSCs in 3D Tri-Copolymer Scaffolds and the Self-Designed Bioreactor System.

机构信息

Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 32001, Taiwan.

Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 10002, Taiwan.

出版信息

Biomolecules. 2021 Jan 16;11(1):115. doi: 10.3390/biom11010115.

Abstract

Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of , , and was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.

摘要

与其他正常组织相比,人类软骨的新陈代谢相对较慢。由于软骨的内在愈合能力有限,因此软骨损伤具有重要的临床意义。软骨组织工程是一个迅速发展的领域,为组织功能修复和人工/工程化组织替代提供了巨大的潜力。然而,目前用于软骨修复的临床疗法并不令人满意,很少能恢复全部功能或使患病组织恢复到其天然健康状态。小分子 Kartogenin(KGN)可以在体外和体内促进软骨细胞的分化。本研究旨在通过 KGN 优化基于间充质干细胞(MSC)的软骨形成构建体中的软骨形成过程,以用于软骨组织工程。在这项研究中,我们证明了 KGN 处理可以促进 MSC 在三聚体支架内的凝聚和细胞簇形成。在三维(3D)培养条件下, 、 和 的表达显著上调。陷窝样结构显示 II 型胶原和聚集蛋白聚糖的沉积活跃。我们期望这些结果将为小分子在与支架结合的软骨分化方案中的应用开辟新途径,这可能为软骨组织工程提供更好的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d988/7829855/d6b67a2fdfe7/biomolecules-11-00115-g001.jpg

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