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Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells
Author(s) -
Lee Jieun,
Taylor Sarah E. B.,
Smeriglio Piera,
Lai Janice,
Maloney William J.,
Yang Fan,
Bhutani Nidhi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-269720
Subject(s) - chondrogenesis , sox9 , induced pluripotent stem cell , microbiology and biotechnology , cartilage , fibrocartilage , extracellular matrix , population , stem cell , chemistry , regenerative medicine , regeneration (biology) , biology , immunology , anatomy , gene expression , articular cartilage , genetics , pathology , medicine , gene , osteoarthritis , embryonic stem cell , alternative medicine , environmental health
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.—Lee, J., Taylor, S. E. B., Smeriglio, P., Lai, J., Maloney, W. J., Yang, F., Bhutani, N. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells. FASEB J. 29, 3399‐3410 (2015). www.fasebj.org