Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
J Cell Biochem. 2013 Feb;114(2):480-90. doi: 10.1002/jcb.24388.
Induced pluripotent stem cells (iPSC) hold tremendous potential for personalized cell-based repair strategies to treat musculoskeletal disorders. To establish human iPSCs as a potential source of viable chondroprogenitors for articular cartilage repair, we assessed the in vitro chondrogenic potential of the pluripotent population versus an iPSC-derived mesenchymal-like progenitor population. We found the direct plating of undifferentiated iPSCs into high-density micromass cultures in the presence of BMP-2 promoted chondrogenic differentiation, however these conditions resulted in a mixed population of cells resembling the phenotype of articular cartilage, transient cartilage, and fibrocartilage. The progenitor cells derived from human iPSCs exhibited immunophenotypic features of mesenchymal stem cells (MSCs) and developed along multiple mesenchymal lineages, including osteoblasts, adipocytes, and chondrocytes in vitro. The data indicate the derivation of a mesenchymal stem cell population from human iPSCs is necessary to limit culture heterogeneity as well as chondrocyte maturation in the differentiated progeny. Moreover, as compared to pellet culture differentiation, BMP-2 treatment of iPSC-derived MSC-like (iPSC-MSC) micromass cultures resulted in a phenotype more typical of articular chondrocytes, characterized by the enrichment of cartilage-specific type II collagen (Col2a1), decreased expression of type I collagen (Col1a1) as well as lack of chondrocyte hypertrophy. These studies represent a first step toward identifying the most suitable iPSC progeny for developing cell-based approaches to repair joint cartilage damage.
诱导多能干细胞（iPSC）在基于细胞的个性化修复策略方面具有巨大的潜力，可用于治疗肌肉骨骼疾病。为了将人类 iPSC 确立为关节软骨修复的可行软骨祖细胞的潜在来源，我们评估了多能细胞群体与 iPSC 衍生的间充质样祖细胞群体的体外软骨形成潜力。我们发现，在 BMP-2 的存在下，将未分化的 iPSC 直接接种到高密度微团培养物中，可促进软骨分化，但这些条件导致了类似于关节软骨、短暂软骨和纤维软骨表型的混合细胞群体。源自人类 iPSC 的祖细胞表现出间充质干细胞（MSC）的免疫表型特征，并在体外沿着多个间充质谱系发育，包括成骨细胞、脂肪细胞和成软骨细胞。这些数据表明，从人类 iPSC 中衍生出间充质干细胞群体对于限制培养异质性以及分化后代中的软骨细胞成熟是必要的。此外，与微团培养分化相比，BMP-2 处理 iPSC 衍生的 MSC 样（iPSC-MSC）微团培养物导致更典型的关节软骨细胞表型，其特征是富含软骨特异性的 II 型胶原（Col2a1），I 型胶原（Col1a1）的表达降低以及缺乏软骨细胞肥大。这些研究代表着朝着确定最适合用于开发基于细胞的方法修复关节软骨损伤的 iPSC 后代迈出的第一步。
