RRC ID |
35177
|
著者 |
Yamashita A, Morioka M, Yahara Y, Okada M, Kobayashi T, Kuriyama S, Matsuda S, Tsumaki N.
|
タイトル |
Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.
|
ジャーナル |
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.
|
巻・号 |
4(3)
|
ページ |
404-18
|
公開日 |
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
|
引用数 |
81
|
WOS 分野
|
CELL & TISSUE ENGINEERING
CELL BIOLOGY
|
リソース情報 |
ラット |
F344-Il2rgem2Kyo (strainID=979) |