Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
PLoS One. 2013 May 23;8(5):e64160. doi: 10.1371/journal.pone.0064160. Print 2013.
Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS) cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS) cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs) in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice.
中风是美国和全球成年人死亡和残疾的主要原因。虽然中风的治疗方法有限，但干细胞移植已成为一种有前途的再生疗法，可以替代或修复受损组织，并增强中风后的功能恢复。最近，通过体细胞重编程产生诱导多能干细胞（iPS 细胞）通过为移植提供无限来源的自体细胞，彻底改变了细胞治疗。此外，无载体和无转基因的人类 iPS（hiPS）细胞的产生提供了新一代的干细胞，降低了与以前技术中观察到的病毒载体随机整合相关的肿瘤形成风险。然而，这些细胞在治疗缺血性中风中的潜在用途尚未得到探索。在本研究中，我们研究了无载体和无转基因的 hiPS 细胞的神经元分化，以及 hiPS 细胞衍生的神经祖细胞（hiPS-NPC）在小鼠缺血性中风模型中的移植。无载体 hiPS 细胞在无饲养细胞和无血清条件下培养，并使用新开发的分化方案在体外分化为功能性神经元。在中风小鼠中移植 28 天后，hiPS-NPC 在体内表现出成熟的神经元标记。移植后 12 个月内未见肿瘤形成。hiPS-NPC 的移植恢复了神经血管偶联，增加了营养支持，并促进了中风后的行为恢复。这些数据表明，使用无载体和无转基因的 hiPS 细胞进行干细胞治疗在增强小鼠局灶性缺血性中风后的恢复方面是安全有效的。
