RRC ID 35177
Author Yamashita A, Morioka M, Yahara Y, Okada M, Kobayashi T, Kuriyama S, Matsuda S, Tsumaki N.
Title Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.
Journal Stem Cell Reports
Abstract Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects.
Volume 4(3)
Pages 404-18
Published 2015-3-10
DOI 10.1016/j.stemcr.2015.01.016
PII S2213-6711(15)00037-5
PMID 25733017
PMC PMC4375934
MeSH Animals Biomarkers Cell Culture Techniques Cell Differentiation* Cell Line Cell Transformation, Neoplastic Chondrocytes / cytology Chondrogenesis Gene Expression Gene Knock-In Techniques Genes, Reporter Humans Hyaline Cartilage / cytology* Hyaline Cartilage / metabolism* Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Mice Mice, SCID Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Stem Cell Transplantation Swine Swine, Miniature Transgenes
IF 6.032
Times Cited 81
WOS Category CELL & TISSUE ENGINEERING CELL BIOLOGY
Resource
Rats F344-Il2rgem2Kyo (strainID=979)