Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells

LING WU; CAROLINA BLUGUERMANN; LEVON KYUPELYAN; BROOKE LATOUR; STEPHANIE GONZALEZ; SAUMUYA SHAH; ZORAN GALIC; SUNDI GE; YUHYA ZHU; ALI NSAIR; FRANK PETRIGLIANO; SANTIAGO G. MIRIUKA; XINMIN LI; KAREN LYONS; DAVID MCALLISTER; GAY CROOKS; BEN VAN HANDEL; JOHN ADAMS; DENIS EVSEENKO

Stem Cell Reports

Elsevier

Año: 2013

2213-6711

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 (CD166low/negCD146low/negCD73+CD44lowBMPR1B+) distinguishing the earliest cartilage committed cells (pre-chondrocytes) at 5-6 weeks of development. From 12 weeks only the superficial layer of articular cartilage was enriched in cells with this pre- chondrocyte/immature chondrocyte phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166low/negBMPR1B+ putative immature chondrocytes. Functional characterization confirmed these cells as committed cartilage progenitors. The identification of a specific molecular signature for the earliest cartilage-committed cells may provide essential knowledge for the generation of clinically relevant cartilage cells from PSCs.