Terzic Dino, Maxon Jacob R, Krevitt Leah, DiBartolomeo Christina, Goyal Tarini, Low Walter C, Dutton James R, Parr Ann M
Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Cell Transplant. 2016;25(2):411-24. doi: 10.3727/096368915X688137. Epub 2015 May 7.
Several neurological disorders, such as multiple sclerosis, the leukodystrophies, and traumatic injury, result in loss of myelin in the central nervous system (CNS). These disorders may benefit from cell-based therapies that prevent further demyelination or are able to restore lost myelin. One potential therapeutic strategy for these disorders is the manufacture of oligodendrocyte progenitor cells (OPCs) by the directed differentiation of pluripotent stem cells, including induced pluripotent stem cells (iPSCs). It has been proposed that OPCs could be transplanted into demyelinated or dysmyelinated regions of the CNS, where they would migrate to the area of injury before terminally differentiating into myelinating oligodendrocytes. OPCs derived from mouse iPSCs are particularly useful for modeling this therapeutic approach and for studying the biology of oligodendrocyte progenitors because of the availability of mouse models of neurological disorders associated with myelin deficiency. Moreover, the utility of miPSC-derived OPCs would be significantly enhanced by the adoption of a consistent, reproducible differentiation protocol that allows OPCs derived from different cell lines to be robustly characterized and compared. Here we describe a standardized, defined protocol that reliably directs the differentiation of miPSCs to generate high yields of OPCs that are capable of maturing into oligodendrocytes.
多种神经系统疾病，如多发性硬化症、脑白质营养不良症和创伤性损伤，会导致中枢神经系统（CNS）髓鞘脱失。这些疾病可能受益于基于细胞的疗法，该疗法可防止进一步的脱髓鞘或能够恢复丢失的髓鞘。针对这些疾病的一种潜在治疗策略是通过多能干细胞（包括诱导多能干细胞（iPSC））的定向分化来制造少突胶质前体细胞（OPC）。有人提出，可以将OPC移植到CNS的脱髓鞘或髓鞘发育异常区域，在那里它们会迁移到损伤区域，然后最终分化为形成髓鞘的少突胶质细胞。由于存在与髓鞘缺乏相关的神经系统疾病的小鼠模型，源自小鼠iPSC的OPC对于模拟这种治疗方法和研究少突胶质前体细胞的生物学特性特别有用。此外，采用一致、可重复的分化方案将显著提高源自小鼠iPSC的OPC的效用，该方案可对源自不同细胞系的OPC进行可靠的表征和比较。在这里，我们描述了一种标准化、明确的方案，该方案能可靠地指导小鼠iPSC的分化，以产生高产量的能够成熟为少突胶质细胞OPC。
