Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy
Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy
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DOI：
10.1038/gt.2011.22
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发表时间：
2011-09-01
期刊：
影响因子：
5.1
通讯作者：
Nishimura, Y.
中科院分区：
文献类型：
--
作者：
Senju, S.;Haruta, M.;Nishimura, Y.
本报告描述了从人诱导多能干细胞（iPS）产生树突状细胞（DC）和巨噬细胞。iPS细胞来源的DC（iPS-DC）具有典型的DC形态和T细胞刺激及抗原提呈功能。负载有巨细胞病毒（CMV）肽的iPS-DC诱导CMV特异性自体CD 8（+）T细胞的剧烈扩增。从iPS细胞中还产生了具有酵母多糖吞噬活性和C5 a诱导的趋化性的巨噬细胞（iPS-MP）。通过将表达载体引入未分化的iPS细胞，分离转染的iPS细胞克隆和随后的分化来产生遗传修饰的iPS-MP。通过这个过程，我们产生了iPS-MP表达特异性淀粉样蛋白β（A β），阿尔茨海默病的致病蛋白的单链抗体（scFv）的膜结合形式。scFv-转染子iPS-MP表现出有效的A β特异性吞噬活性。表达CD 20特异性scFv的iPS-MP吞噬并杀死BALL-1 B细胞白血病细胞。在使用严重联合免疫缺陷小鼠的异种移植模型中证明了iPS-MP的体内抗BALL-1作用。此外，我们建立了无异种培养方案以产生iPS-DC和iPS-MP。总之，我们证明了iPS-DC和巨噬细胞应用于细胞治疗的可能性。Gene Therapy（2011）18，874-883; doi：10.1038/gt.2011.22; 2011年3月24日在线发表
This report describes generation of dendritic cells (DCs) and macrophages from human induced pluripotent stem (iPS) cells. iPS cell-derived DC (iPS-DC) exhibited the morphology of typical DC and function of T-cell stimulation and antigen presentation. iPS-DC loaded with cytomegalovirus (CMV) peptide induced vigorous expansion of CMV-specific autologous CD8(+) T cells. Macrophages (iPS-MP) with activity of zymosan phagocytosis and C5a-induced chemotaxis were also generated from iPS cells. Genetically modified iPS-MPs were generated by the introduction of expression vectors into undifferentiated iPS cells, isolation of transfectant iPS cell clone and subsequent differentiation. By this procedure, we generated iPS-MP expressing a membrane-bound form of single chain antibody (scFv) specific to amyloid beta (A beta), the causal protein of Alzheimer's disease. The scFv-transfectant iPS-MP exhibited efficient A beta-specific phagocytosis activity. iPS-MP expressing CD20-specific scFv engulfed and killed BALL-1 B-cell leukemia cells. Anti-BALL-1 effect of iPS-MP in vivo was demonstrated in a xeno-transplantation model using severe combined immunodeficient mice. In addition, we established a xeno-free culture protocol to generate iPS-DC and iPS-MP. Collectively, we demonstrated the possibility of application of iPS-DC and macrophages to cell therapy. Gene Therapy (2011) 18, 874-883; doi:10.1038/gt.2011.22; published online 24 March 2011