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用于软骨修复的干细胞:临床前研究以及对转化动物模型和结果指标的见解

Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

作者信息

Lo Monaco Melissa, Merckx Greet, Ratajczak Jessica, Gervois Pascal, Hilkens Petra, Clegg Peter, Bronckaers Annelies, Vandeweerd Jean-Michel, Lambrichts Ivo

机构信息

Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Campus Diepenbeek, 3590 Diepenbeek, Belgium.

Department of Veterinary Medicine, Integrated Veterinary Research Unit-Namur Research Institute for Life Science (IVRU-NARILIS), Faculty of Sciences, University of Namur, 5000 Namur, Belgium.

出版信息

Stem Cells Int. 2018 Feb 5;2018:9079538. doi: 10.1155/2018/9079538. eCollection 2018.

DOI:10.1155/2018/9079538
PMID:29535784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5832141/
Abstract

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent data and from preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

摘要

由于损伤后软骨细胞再生丢失软骨的内在能力有限,基于干细胞的疗法已被提出作为软骨修复的一种新型治疗方法。此外,使用间充质干细胞(MSCs)或诱导多能干细胞(iPSCs)的基于干细胞的疗法已在临床前和临床环境中成功应用。尽管有这些令人鼓舞的报道,但干细胞介导软骨修复的确切机制仍不确定。干细胞可通过软骨生成分化、免疫调节或通过产生旁分泌因子和细胞外囊泡促进软骨修复。但在将新型基于细胞的软骨修复疗法引入临床之前,需要在临床前动物模型中进行严格测试。用于再生软骨研究的临床前模型包括小鼠、兔、山羊、绵羊、猪、犬和马模型,每种模型都有其特定的优点和局限性。本综述总结了近期临床前研究的数据,证明了MSCs和iPSCs在软骨组织工程中的应用。此外,还将讨论使用小型和大型动物的优缺点,同时描述评估软骨修复的合适结果指标。

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