Generation of Scaffoldless Hyaline Cartilaginous Tissue from Human iPSCs

被引：195

作者：

Yamashita, Akihiro ^{[1
]}

Morioka, Miho ^{[1
]}

Yahara, Yasuhito ^{[1
]}

Okada, Minoru ^{[1
]}

Kobayashi, Tomohito ^{[1
,2
]}

Kuriyama, Shinichi ^{[2
]}

Matsuda, Shuichi ^{[2
]}

Tsumaki, Noriyuki ^{[1
,3
]}

机构：

[1] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Cell Induct & Regulat Field, Kyoto 6068507, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Orthopaed Surg, Kyoto 6068507, Japan

[3] Japan Sci & Technol Agcy, CREST, Tokyo 1020075, Japan

来源：

STEM CELL REPORTS | 2015年 / 4卷 / 03期

基金：

日本学术振兴会;

关键词：

EMBRYONIC STEM-CELLS; CHONDROGENIC DIFFERENTIATION; DIRECTED SPECIFICATION; IN-VITRO; REPAIR; BONE; CHONDROCYTES; INTEGRATION; RECEPTORS; INDUCTION;

D O I：

10.1016/j.stemcr.2015.01.016

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 beta 1 (TGF-beta 1), 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 immuno-suppressed 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.

引用

页码：404 / 418

页数：15

共 35 条

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