UMR 7365 CNRS-UL IMoPA, Universite de Lorraine, Nancy, France.
Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg, Germany.
Curr Stem Cell Res Ther. 2019;14(4):337-343. doi: 10.2174/1574888X14666181205121658.
Musculoskeletal pathologies, especially those affecting bones and joints, remain a challenge for regenerative medicine. The main difficulties affecting bone tissue engineering are the size of the defects, the need for blood vessels and the synthesis of appropriate matrix elements in the engineered tissue. Indeed, the cartilage is an avascular tissue and consequently has limited regenerative abilities. Thanks to their self-renewal, plasticity and immunomodulatory properties, mesenchymal stem cells (MSCs) became a central player in tissue engineering, and have already been shown to be able to differentiate towards chondrogenic or osteogenic phenotypes. Whether synthetic (e.g. tricalcium phosphate) or from natural sources (e.g. hyaluronic acid), biomaterials can be shaped to fit into bone and cartilage defects to ensure mechanical resistance and may also be designed to control cell spatial distribution or differentiation. Soluble factors are classically used to promote cell differentiation and to stimulate extracellular matrix synthesis to achieve the desired tissue production. But as they have a limited lifetime, transfection using plasmid DNA or transduction via a viral vector of therapeutic genes to induce the cell secretion of these factors allows to have more lasting effects. Also, the chondrocyte phenotype may be difficult to control over time, with for example the production of hypertrophic or osteogenic markers that is undesirable in hyaline cartilage. Thus, tissue regeneration strategies became more elaborate, with an attempt at associating the benefits of MSCs, biomaterials, and gene therapy to achieve a proper tissue repair. This minireview focuses on in vitro and in vivo studies combining biomaterials and gene therapy associated with MSCs for bone and cartilage engineering.
肌肉骨骼病理学，特别是影响骨骼和关节的病理学，仍然是再生医学面临的挑战。影响骨组织工程的主要困难是缺陷的大小、血管的需求以及工程组织中适当基质元素的合成。事实上，软骨是一种无血管组织，因此再生能力有限。间充质干细胞（MSCs）由于其自我更新、可塑性和免疫调节特性，成为组织工程的核心参与者，并且已经能够向软骨或成骨表型分化。生物材料无论是合成的（例如磷酸三钙）还是天然来源的（例如透明质酸），都可以被塑造成适合骨和软骨缺陷的形状，以确保机械抗性，并且还可以设计为控制细胞空间分布或分化。可溶性因子通常用于促进细胞分化和刺激细胞外基质合成，以实现所需的组织产生。但是，由于它们的寿命有限，使用质粒 DNA 转染或通过病毒载体转导治疗基因来诱导细胞分泌这些因子可以产生更持久的效果。此外，软骨细胞表型可能难以随时间控制，例如产生不希望在透明软骨中出现的肥大或成骨标志物。因此，组织再生策略变得更加复杂，试图结合 MSCs、生物材料和基因治疗的优势，以实现适当的组织修复。这篇小型综述重点介绍了将生物材料和基因治疗与 MSCs 结合用于骨和软骨工程的体外和体内研究。
