Honsho Kimiko, Hirose Michiko, Hatori Masanori, Yasmin Lubna, Izu Haruna, Matoba Shogo, Togayachi Sumie, Miyoshi Hiroyuki, Sankai Tadashi, Ogura Atsuo, Honda Arata
Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan.
J Reprod Dev. 2015;61(1):13-9. doi: 10.1262/jrd.2014-098. Epub 2014 Oct 25.
Quality evaluation of pluripotent stem cells using appropriate animal models needs to be improved for human regenerative medicine. Previously, we demonstrated that although the in vitro neural differentiating capacity of rabbit induced pluripotent stem cells (iPSCs) can be mitigated by improving their baseline level of pluripotency, i.e., by converting them into the so-called "naïve-like" state, the effect after such conversion of rabbit embryonic stem cells (ESCs) remains to be elucidated. Here we found that naïve-like conversion enhanced the differences in innate in vitro differentiation capacity between ESCs and iPSCs. Naïve-like rabbit ESCs exhibited several features indicating pluripotency, including the capacity for teratoma formation. They differentiated into mature oligodendrocytes much more effectively (3.3-7.2 times) than naïve-like iPSCs. This suggests an inherent variation in differentiation potential in vitro among PSC lines. When naïve-like ESCs were injected into preimplantation rabbit embryos, although they contributed efficiently to forming the inner cell mass of blastocysts, no chimeric pups were obtained. Thus, in vitro neural differentiation following naïve-like conversion is a promising option for determining the quality of PSCs without the need to demonstrate chimeric contribution. These results provide an opportunity to evaluate which pluripotent stem cells or treatments are best suited for therapeutic use.
对于人类再生医学而言，使用合适的动物模型对多能干细胞进行质量评估仍有待改进。此前，我们证明，虽然兔诱导多能干细胞（iPSC）的体外神经分化能力可通过提高其多能性基线水平（即将其转化为所谓的“类原始态”）而得到改善，但兔胚胎干细胞（ESC）经此类转化后的效果仍有待阐明。在此，我们发现类原始态转化增强了ESC和iPSC之间先天体外分化能力的差异。类原始态兔ESC表现出多种表明多能性的特征，包括形成畸胎瘤的能力。它们分化为成熟少突胶质细胞的效率比类原始态iPSC高得多（3.3至7.2倍）。这表明PSC系之间在体外分化潜能方面存在内在差异。当将类原始态ESC注射到植入前兔胚胎中时，尽管它们有效地参与形成囊胚的内细胞团，但未获得嵌合幼崽。因此，类原始态转化后的体外神经分化是一种有前景的选择，可用于确定PSC的质量，而无需证明嵌合贡献。这些结果为评估哪些多能干细胞或治疗方法最适合治疗用途提供了契机。
