1 Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA.
2 Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Cell Transplant. 2017 Dec;26(12):1890-1902. doi: 10.1177/0963689717737074.
The use of defined conditions for derivation, maintenance, and differentiation of human-induced pluripotent stem cells (hiPSCs) provides a superior experimental platform to discover culture responses to differentiation cues and elucidate the basic requirements for cell differentiation and fate restriction. Adoption of defined systems for reprogramming, undifferentiated growth, and differentiation of hiPSCs was found to significantly influence early stage differentiation signaling requirements and temporal kinetics for the production of primitive neuroectoderm. The bone morphogenic protein receptor agonist LDN-193189 was found to be necessary and sufficient for neural induction in a monolayer system with landmark antigens paired box 6 and sex-determining region Y-box 1 appearing within 72 h. Preliminary evidence suggests this neuroepithelium was further differentiated to generate ventral spinal neural progenitors that produced electrophysiologically active neurons in vitro, maintaining viability posttransplantation in an immunocompromised host. Our findings support current developments in the field, demonstrating that adoption of defined reagents for the culture and manipulation of pluripotent stem cells is advantages in terms of simplification and acceleration of differentiation protocols, which will be critical for future clinical translation.
使用定义明确的条件来衍生、维持和分化人类诱导多能干细胞（hiPSCs），为发现培养物对分化信号的反应以及阐明细胞分化和命运限制的基本要求提供了一个优越的实验平台。采用定义明确的系统进行重编程、未分化生长和 hiPSC 的分化，发现这显著影响了早期分化信号要求和原始神经外胚层产生的时间动力学。骨形态发生蛋白受体激动剂 LDN-193189 被发现对于单层系统中的神经诱导是必要且充分的，标志性抗原配对盒 6 和性别决定区 Y 盒 1 在 72 小时内出现。初步证据表明，这种神经上皮进一步分化为产生在体外产生电生理活性神经元的腹侧脊髓神经祖细胞，并在免疫缺陷宿主中移植后保持存活。我们的发现支持该领域的当前发展，表明采用定义明确的试剂来培养和操作多能干细胞在简化和加速分化方案方面具有优势，这对于未来的临床转化至关重要。
