Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM2-UM1, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM2-UM1, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France; Ecole Pratique des Hautes Etudes, PSL Research University, 75014 Paris, France.
Biomaterials. 2016 Oct;104:223-37. doi: 10.1016/j.biomaterials.2016.07.017. Epub 2016 Jul 21.
Recent regenerative medicine and tissue engineering strategies for bone and cartilage repair have led to fascinating progress of translation from basic research to clinical applications. In this context, the use of gene therapy is increasingly being considered as an important therapeutic modality and regenerative technique. Indeed, in the last 20 years, nucleic acids (plasmid DNA, interferent RNA) have emerged as credible alternative or complement to proteins, which exhibited major issues including short half-life, loss of bioactivity in pathologic environment leading to high dose requirement and therefore high production costs. The relevance of gene therapy strategies in combination with a scaffold, following a so-called "Gene-Activated Matrix (GAM)" approach, is to achieve a direct, local and sustained delivery of nucleic acids from a scaffold to ensure efficient and durable cell transfection. Among interesting cells sources, Mesenchymal Stem Cells (MSC) are promising for a rational use in gene/cell therapy with more than 1700 clinical trials approved during the last decade. The aim of the present review article is to provide a comprehensive overview of recent and ongoing work in non-viral genetic engineering of MSC combined with scaffolds. More specifically, we will show how this inductive strategy can be applied to orient stem cells fate for bone and cartilage repair.
近年来，骨和软骨修复的再生医学和组织工程策略取得了令人瞩目的进展，基础研究向临床应用的转化取得了进展。在这种情况下，基因治疗的应用越来越被认为是一种重要的治疗方式和再生技术。事实上，在过去的 20 年中，核酸（质粒 DNA、干扰 RNA）已经成为蛋白质的可靠替代品或补充物，蛋白质存在半衰期短、在病理环境中失去生物活性导致需要高剂量和因此高生产成本等主要问题。基因治疗策略与支架结合的相关性，采用所谓的“基因激活基质（GAM）”方法，是为了实现从支架直接、局部和持续输送核酸，以确保有效的和持久的细胞转染。在有趣的细胞来源中，间充质干细胞（MSC）是基因/细胞治疗的有前途的选择，在过去十年中批准了超过 1700 项临床试验。本文综述的目的是对与支架结合的 MSC 的非病毒基因工程的最新和正在进行的工作进行全面概述。更具体地说，我们将展示这种诱导策略如何应用于引导干细胞的命运以修复骨和软骨。
