Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage

Daisuke Kamiya; Nana Takenaka-Ninagawa; Souta Motoike; Mikihito Kajiya; Teppei Akaboshi; Chengzhu Zhao; Mitsuaki Shibata; Sho Senda; Yayoi Toyooka; Hidetoshi Sakurai; Hidemi Kurihara; Makoto Ikeya

doi:10.1038/s41536-022-00241-8

Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage

NPJ Regen Med. 2022 Sep 15;7(1):47. doi: 10.1038/s41536-022-00241-8.

Authors

Daisuke Kamiya^{1

2}, Nana Takenaka-Ninagawa¹, Souta Motoike^{1

3}, Mikihito Kajiya³, Teppei Akaboshi^{1

2}, Chengzhu Zhao¹, Mitsuaki Shibata¹, Sho Senda⁴, Yayoi Toyooka^{1

2}, Hidetoshi Sakurai¹, Hidemi Kurihara³, Makoto Ikeya^{5

6}

Affiliations

¹ Dept. of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
² Takeda-CiRA Joint Program, Fujisawa, Kanagawa , Japan.
³ Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
⁴ Research Institute for Bioscience Product & Fine Chemicals, Ajinomoto Co., Inc., Kawasaki, 210-8681, Japan.
⁵ Dept. of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. mikeya@cira.kyoto-u.ac.jp.
⁶ Takeda-CiRA Joint Program, Fujisawa, Kanagawa , Japan. mikeya@cira.kyoto-u.ac.jp.

Abstract

Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells. Here, we induced MSCs from human induced pluripotent stem cells (iPSCs) via a neural crest cell (NCC) lineage under xeno-free conditions and evaluated their in vivo functions. We modified a previous MSC induction method to work under xeno-free conditions. Bovine serum albumin-containing NCC induction medium and fetal bovine serum-containing MSC induction medium were replaced with xeno-free medium. Through our optimized method, iPSCs differentiated into MSCs with high efficiency. To evaluate their in vivo activities, we transplanted the xeno-free-induced MSCs (XF-iMSCs) into mouse models for bone and skeletal muscle regeneration and confirmed their regenerative potency. These XF-iMSCs mainly promoted the regeneration of surrounding host cells, suggesting that they secrete soluble factors into affected regions. We also found that the peroxidasin and IGF2 secreted by the XF-iMSCs partially contributed to myotube differentiation. These results suggest that XF-iMSCs are important for future applications in regenerative medicine.

Abstract

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