Sugai Keiko, Fukuzawa Ryuji, Shofuda Tomoko, Fukusumi Hayato, Kawabata Soya, Nishiyama Yuichiro, Higuchi Yuichiro, Kawai Kenji, Isoda Miho, Kanematsu Daisuke, Hashimoto-Tamaoki Tomoko, Kohyama Jun, Iwanami Akio, Suemizu Hiroshi, Ikeda Eiji, Matsumoto Morio, Kanemura Yonehiro, Nakamura Masaya, Okano Hideyuki
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, 160-8582, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
Mol Brain. 2016 Sep 19;9(1):85. doi: 10.1186/s13041-016-0265-8.
The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.
致瘤风险是利用诱导多能干细胞（iPSC）进行再生医学面临的一个障碍。虽然畸胎瘤的形成很容易辨别，但由于对组织学和表型的分析不足，iPSC衍生物的恶性转化尚未得到明确界定。在本研究中，我们评估了将无整合的人外周血单核细胞（PBMC）来源的iPSC（iPSC-NSPC）生成的神经干/祖细胞（NSPC）移植到免疫缺陷小鼠中枢神经系统（CNS）后其组织学情况。我们发现，移植的iPSC-NSPC产生的分化模式类似于胚胎中枢神经系统发育中的模式，并且迁移最终部位的微环境影响它们的成熟阶段。iPSC的基因组不稳定性与移植细胞增殖增加相关，尽管未发现明显的致癌现象。此处呈现的组织学分类可能为解决涉及iPSC的再生医学面临的潜在安全问题提供线索。
