Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

• DOI: 10.1016/j.stemcr.2013.10.012
• Publication Date: 2013-12-13T02:02:52Z
• Authors: Ling Wu; Carolina Bluguermann; Levon Kyupelyan; Brooke Latour; Stephanie Gonzalez; Saumya Shah; Zoran Galic; Sundi Ge; Yuhua Zhu; Frank A. Petrigliano; Ali Nsair; Santiago G. Miriuka; Xinmin Li; Karen M. Lyons; Gay M. Crooks; David R. McAllister; Ben Van Handel; John S. Adams; Denis Evseenko
• Keywords: Cartilage, Articular; Pluripotent Stem Cells; 0301 basic medicine; Aging; 571; Cells; Clinical Sciences; Cell Culture Techniques; Laser Capture Microdissection; Regenerative Medicine; Article; DEVELOPMENT; 03 medical and health sciences; Chondrocytes; CHONDROGENESIS; Stem Cell Research - Nonembryonic - Human; https://purl.org/becyt/ford/1.6; Humans; Developmental; Cell Lineage; Stem Cell Research - Embryonic - Human; https://purl.org/becyt/ford/1; PLURIPOTENT; Cells, Cultured; Oligonucleotide Array Sequence Analysis; Cultured; Stem Cell Research - Induced Pluripotent Stem Cell - Human; Stem Cell Research - Induced Pluripotent Stem Cell; Tissue Engineering; Arthritis; HUMAN; Gene Expression Regulation, Developmental; Cell Differentiation; Biological Sciences; Stem Cell Research; Flow Cytometry; Cartilage; Gene Expression Regulation; Musculoskeletal; Biochemistry and cell biology; Stem Cell Research - Nonembryonic - Non-Human; Biochemistry and Cell Biology; Chondrogenesis; Biomarkers; Biotechnology; Articular

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.