Kamiya Daisuke, Takenaka-Ninagawa Nana, Motoike Souta, Kajiya Mikihito, Akaboshi Teppei, Zhao Chengzhu, Shibata Mitsuaki, Senda Sho, Toyooka Yayoi, Sakurai Hidetoshi, Kurihara Hidemi, Ikeya Makoto
Dept. of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Takeda-CiRA Joint Program, Fujisawa, Kanagawa , Japan.
NPJ Regen Med. 2022 Sep 15;7(1):47. doi: 10.1038/s41536-022-00241-8.
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.
间充质干/基质细胞（MSCs）是成体多能干细胞。在此，我们在无血清条件下通过神经嵴细胞（NCC）谱系从人诱导多能干细胞（iPSCs）诱导生成MSCs，并评估了它们的体内功能。我们改进了先前的MSC诱导方法，使其能在无血清条件下工作。含牛血清白蛋白的NCC诱导培养基和含胎牛血清的MSC诱导培养基被无血清培养基所取代。通过我们优化的方法，iPSCs高效分化为MSCs。为了评估它们的体内活性，我们将无血清诱导的MSCs（XF-iMSCs）移植到用于骨和骨骼肌再生的小鼠模型中，并证实了它们的再生能力。这些XF-iMSCs主要促进周围宿主细胞的再生，表明它们向受影响区域分泌可溶性因子。我们还发现，XF-iMSCs分泌的过氧化物酶和IGF2部分促进了肌管分化。这些结果表明，XF-iMSCs对再生医学的未来应用具有重要意义。
