J Biomed Mater Res A. 2019 Jan 21. doi: 10.1002/jbm.a.36615. [Epub ahead of print]

Chondrogenic differentiation of mouse induced pluripotent stem cells (iPSCs) using the three-dimensional culture with ultra-purified alginate gel (UPAL gel).

Hontani K¹, Onodera T¹, Terashima M¹, Momma D¹, Matsuoka M¹, Baba R¹, Joutoku Z¹, Matsubara S¹, Homan K¹, Hishimura R¹, Xu L¹, Iwasaki N¹.

Abstract

Since articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs by using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the up-regulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. This article is protected by copyright. All rights reserved.