Somoza Rodrigo A, Welter Jean F, Correa Diego, Caplan Arnold I
Department of Biology, Skeletal Research Center, Case Western Reserve University , Cleveland, Ohio.
Tissue Eng Part B Rev. 2014 Dec;20(6):596-608. doi: 10.1089/ten.TEB.2013.0771. Epub 2014 May 27.
Articular cartilage repair and regeneration provides a substantial challenge in Regenerative Medicine because of the high degree of morphological and mechanical complexity intrinsic to hyaline cartilage due, in part, to its extracellular matrix. Cartilage remains one of the most difficult tissues to heal; even state-of-the-art regenerative medicine technology cannot yet provide authentic cartilage resurfacing. Mesenchymal stem cells (MSCs) were once believed to be the panacea for cartilage repair and regeneration, but despite years of research, they have not fulfilled these expectations. It has been observed that MSCs have an intrinsic differentiation program reminiscent of endochondral bone formation, which they follow after exposure to specific reagents as a part of current differentiation protocols. Efforts have been made to avoid the resulting hypertrophic fate of MSCs; however, so far, none of these has recreated a fully functional articular hyaline cartilage without chondrocytes exhibiting a hypertrophic phenotype. We reviewed the current literature in an attempt to understand why MSCs have failed to regenerate articular cartilage. The challenges that must be overcome before MSC-based tissue engineering can become a front-line technology for successful articular cartilage regeneration are highlighted.
关节软骨修复与再生在再生医学中是一项重大挑战，因为透明软骨固有的形态和力学复杂性很高，部分原因在于其细胞外基质。软骨仍然是最难愈合的组织之一；即使是最先进的再生医学技术也尚未能实现真正的软骨表面修复。间充质干细胞（MSCs）曾被认为是软骨修复与再生的万灵药，但尽管经过多年研究，它们并未达到这些期望。据观察，MSCs具有类似于软骨内成骨的内在分化程序，在接触特定试剂后，它们会按照当前分化方案的一部分遵循该程序。人们已努力避免MSCs最终出现肥大的命运；然而，到目前为止，尚无一种方法能在不使软骨细胞表现出肥大表型的情况下重新创建出功能完全正常的关节透明软骨。我们回顾了当前的文献，试图理解为什么MSCs未能再生关节软骨。强调了在基于MSCs的组织工程成为成功的关节软骨再生一线技术之前必须克服的挑战。
