Nori Satoshi, Tsuji Osahiko, Okada Yohei, Toyama Yoshiaki, Okano Hideyuki, Nakamura Masaya
Department of Orthopaedic Surgery, Keio University School of Medicine.
Brain Nerve. 2012 Jan;64(1):17-27.
Once the safety issue has been overcome, induced pluripotent stem cells (iPSCs), which do not entail ethical or immunological concerns, may become the preferred cell source for regenerative medicine. Various types of iPSCs have been established by different methods, and each type exhibits different biological properties. Before iPSC-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Recently, we demonstrated the directed neural differentiation of mouse iPSCs and examined their therapeutic potential in a mouse spinal cord injury (SCI) model. Mouse iPSC-derived neural stem/progenitor cells (NS/PCs), which had been pre-evaluated as non-tumorigenic by their transplantation into nonobese diabetic-severe combined immunodeficiency (NOD-scid) mouse brain, were transplanted into the spinal cord 9 days after SCI. Mouse iPSC-derived NS/PCs differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in re-myelination and induced the axonal re-growth, promoting motor functional recovery. Nevertheless, our results constitute only the first step toward clinical application. The safety and effectiveness of human iPSC-derived NS/PCs need to be more intensively investigated in future preclinical studies, for example, using non-human primate SCI models. In particular, human iPSCs established by delivering reprogramming factors using a safer method than retrovirus system, such as an integration-free virus system, virus-free system, or transgene-free system should be evaluated.
一旦安全问题得到解决,诱导多能干细胞(iPSC)可能会成为再生医学中首选的细胞来源,因为它不存在伦理或免疫方面的问题。人们通过不同方法建立了多种类型的iPSC,每种类型都具有不同的生物学特性。在基于iPSC的临床应用开始之前,应对这些细胞进行详细评估,包括它们在不同环境下的分化潜能和致瘤活性,以确定其用于细胞移植治疗的安全性和有效性。最近,我们展示了小鼠iPSC向神经细胞的定向分化,并在小鼠脊髓损伤(SCI)模型中研究了它们的治疗潜力。将预先评估为无致瘤性的小鼠iPSC衍生的神经干细胞/祖细胞(NS/PC)移植到非肥胖糖尿病-严重联合免疫缺陷(NOD-scid)小鼠脑内后,于脊髓损伤9天后将其移植到脊髓中。小鼠iPSC衍生的NS/PC分化为所有三种神经谱系,未形成畸胎瘤或其他肿瘤。它们还参与了髓鞘再生并诱导轴突再生,促进运动功能恢复。然而,我们的结果仅仅是迈向临床应用的第一步。未来的临床前研究需要更深入地研究人iPSC衍生的NS/PC的安全性和有效性,例如使用非人灵长类动物SCI模型。特别是,应该评估通过比逆转录病毒系统更安全的方法(如无整合病毒系统、无病毒系统或无转基因系统)导入重编程因子所建立的人iPSC。