Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Laboratorio de Biología del Desarrollo Celular, Laboratorios de Investigación Aplicada en Nuerociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Escobar B1625XAF, Buenos Aires, Argentina.
Stem Cell Reports. 2013 Dec 12;1(6):575-89. doi: 10.1016/j.stemcr.2013.10.012. eCollection 2013.
Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.
关节损伤和骨关节炎影响着全球数以百万计的人，但利用成体干细胞/祖细胞生成关节软骨的尝试均未成功。我们假设利用多能干细胞（PSCs）重现人类发育性软骨生成程序可能是软骨修复的一种更优方法。我们首先使用激光捕获显微切割和微阵列分析，定义了一个表面表型（CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)），用于区分发育 5-6 周时最早的软骨定向细胞（前软骨细胞）。功能研究证实这些细胞是软骨细胞祖细胞。从 12 周开始，只有关节软骨的浅层富含具有这种祖细胞表型的细胞。从分化的人 PSCs 中分离出具有类似免疫表型的细胞，揭示了一群 CD166(low/neg)BMPR1B(+)的假定软骨定向祖细胞。总而言之，这些数据定义了一种从 PSCs 生成高度纯化的功能性人软骨细胞的发育方法，这可能会推动软骨组织工程的重大进展。
