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- Title
Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells.
- Authors
Jieun Lee; Taylor, Sarah E. B.; Smeriglio, Piera; Lai, Janice; Maloney, William J.; Fan Yang; Bhutani, Nidhi
- Abstract
Regeneration of human cartilage is inherently inefficient; an abundant autologous source, such as human induced pluripotent stem cells (hiPSCs), is therefore attractive for engineering cartilage. We report a growth factor-based protocol for differentiating hiPSCs into articular-like chondrocytes (hiChondrocytes) within 2 weeks, with an overall efficiency >90%. The hiChondrocytes are stable and comparable to adult articular chondrocytes in global gene expression, extracellular matrix production, and ability to generate cartilage tissue in vitro and in immune-deficient mice. Molecular characterization identified an early SRY (sex-determining region Y) box (Sox)9low cluster of differentiation (CD)44lowCD140low prechondrogenic population during hiPSC differentiation. In addition, 2 distinct Sox9-regulated gene networks were identified in the Sox9low and Sox9high populations providing novel molecular insights into chondrogenic fate commitment and differentiation. Our findings present a favorable method for generating hiPSC-derived articular-like chondrocytes. The hiChondrocytes are an attractive cell source for cartilage engineering because of their abundance, autologous nature, and potential to generate articular-like cartilage rather than fibrocartilage. In addition, hiChondrocytes can be excellent tools for modeling human musculoskeletal diseases in a dish and for rapid drug screening.
- Subjects
PLURIPOTENT stem cells; CARTILAGE physiology; CARTILAGE cells; GENE expression; CELL physiology
- Publication
FASEB Journal, 2015, Vol 29, Issue 8, p3399
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-269720