Differentiation of human and murine induced pluripotent stem cells to microglia-like cells.
Differentiation of human and murine induced pluripotent stem cells to microglia-like cells.
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DOI：
10.1038/nn.4534
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发表时间：
2017-05
影响因子：
25
通讯作者：
Park JK
中科院分区：
文献类型：
--
作者：
Pandya H;Shen MJ;Ichikawa DM;Sedlock AB;Choi Y;Johnson KR;Kim G;Brown MA;Elkahloun AG;Maric D;Sweeney CL;Gossa S;Malech HL;McGavern DB;Park JK
小胶质细胞是中枢神经系统（CNS）的常驻炎性细胞，在发育、稳态和各种神经和精神疾病中具有重要作用。获取人类小胶质细胞的困难限制了他们的研究，并阻碍了在动物疾病模型中有效的基于小胶质细胞的治疗的临床转化。在这里，我们报告的人诱导多能干细胞（iPSC）分化成小胶质细胞样细胞暴露于定义的因素和共培养星形胶质细胞。这些iPSC衍生的小胶质细胞（iPS-MG）具有脑分离的小胶质细胞的表型、基因表达谱和功能特性。使用类似方案产生的鼠iPS-MG在治疗鼠同基因颅内恶性胶质瘤中具有与原代脑分离的小胶质细胞等同的功效。产生人类小胶质细胞的能力促进了对这种重要的CNS细胞类型的进一步研究，并提高了它们在个性化医学应用中使用的可能性。
Microglia are the resident inflammatory cells of the central nervous system (CNS) and have important roles in development, homeostasis and a variety of neurologic and psychiatric diseases. Difficulties in procuring human microglia have limited their study and hampered the clinical translation of microglia-based treatments shown to be effective in animal disease models. Here, we report the differentiation of human induced pluripotent stem cells (iPSC) into microglia-like cells by exposure to defined factors and co-culture with astrocytes. These iPSC-derived microglia (iPS-MG) have the phenotype, gene expression profile and functional properties of brain-isolated microglia. Murine iPS-MG generated using a similar protocol have equivalent efficacy to primary brain-isolated microglia in the treatment of murine syngeneic intracranial malignant gliomas. The ability to generate human microglia facilitates the further study of this important CNS cell type and raises the possibility of their use in personalized medicine applications.