Stem Cells Dev. 2018 Sep 25. doi: 10.1089/scd.2018.0058. [Epub ahead of print]

Immunological properties of neural crest cells derived from human induced pluripotent stem cells.

Fujii S¹, Yoshida S^2,3, Inagaki E⁴, Hatou S⁵, Tsubota K⁶, Takahashi M⁷, Shimmura S⁸, Sugita S⁹.

Abstract

Collecting sufficient quantities of primary neural crest cells (NCCs) for experiments is difficult, as NCCs are embryonic transient tissue that basically does not proliferate. We successfully induced NCCs from human induced pluripotent stem cells (iPSCs) in accordance with a previously described method with some modifications. The protocol used in this study efficiently produced large amounts of iPSC-derived NCCs (iPSC-NCCs). Many researchers have recently produced large amounts of iPSC-NCCs and used these to examine the physiological properties, such as migratory activity, and the potential for medical uses such as wound healing. Immunological properties of neural crest cells have yet to be reported. Therefore, the purpose of this study was to assess the immunological properties of human iPSC-NCCs. Our current study showed that iPSC-NCCs were hypoimmunogenic and had immunosuppressive properties in vitro. Expression of HLA class I molecules on iPSC-NCCs was lower than that observed for iPSCs, and there was no expression of HLA class II and co-stimulatory molecules on the cells. With regard to the immunosuppressive properties, iPSC-NCCs greatly inhibited T-cell activation (cell proliferation, production of inflammatory cytokines) after stimulation. iPSC-NCCs constitutively expressed membrane-bound TGF-β, and TGF-β produced by iPSC-NCCs played a critical role in T cell suppression. Thus, cultured human NCCs can fully suppress T-cell activation in vitro. This study may contribute to the realization of using stem cell-derived NCCs in cell-based medicine.