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FASEB J. 2015 Aug;29(8):3399-410. doi: 10.1096/fj.14-269720. Epub 2015 Apr 24.

Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells.

Author information

1
*Department of Orthopaedic Surgery, Department of Mechanical Engineering, and Department of Bioengineering, Stanford University School of Medicine, Stanford, California, USA.
2
*Department of Orthopaedic Surgery, Department of Mechanical Engineering, and Department of Bioengineering, Stanford University School of Medicine, Stanford, California, USA nbhutani@stanford.edu.

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)9(low) cluster of differentiation (CD)44(low)CD140(low) prechondrogenic population during hiPSC differentiation. In addition, 2 distinct Sox9-regulated gene networks were identified in the Sox9(low) and Sox9(high) 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.

KEYWORDS:

cartilage regeneration; hiPSC-derived chondrocytes; prechondrogenic population

PMID:
25911615
PMCID:
PMC4511207
DOI:
10.1096/fj.14-269720
[Indexed for MEDLINE]
Free PMC Article

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