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干细胞在疾病治疗中的应用
Stem Cells in the Treatment of Disease


Helen M. Blau ... 其他 • 2019.05.02
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诱导多能干细胞(iPSC)的获得已经彻底改变了干细胞研究(本文使用的缩略语表请参见下文中的表格)。像胚胎干细胞(ESC)一样,iPSC可无限增殖,并且基本上可分化成任何特定的细胞类型。与ESC不同,iPSC是从体细胞产生的,避免了伦理争议,为发病机制和药物筛选研究提供了患者来源的疾病模型,也为实验性移植疗法提供了细胞来源。一般而言,产生iPSC的方法是在容易获得、完全分化的细胞(例如血液、皮肤或尿液中的细胞)中使四种转录因子瞬时超表达(图1)。由此产生的细胞证明了细胞命运的可塑性1,2、重新表达了端粒酶并且恢复了端粒长度和“重置”了表观遗传景观,这些特征与永生化细胞系相关3

 

缩略语表 

 

图1. 干细胞的类型

具有自我更新和特定组织修复能力的组织特异性“成体”干细胞驻留在某些组织中,例如表皮、角膜缘组织、骨骼肌和血液。多能干细胞(PSC)包括来源于胚泡的胚胎干细胞(ESC)和人诱导多能干细胞(iPSC),产生iPSC的方法是在培养物内,在容易获得的细胞(例如血液、皮肤或尿液中的细胞)中使四种转录因子超表达,从而使这些细胞永生。患者特异性人iPSC可在体外广泛增殖并分化成不同的细胞,例如心肌细胞或神经元,以便在培养物中建立疾病模型、筛选药物、在疾病的临床前小鼠研究中检验功能,并最终应用于临床。我们也可通过候选药物刺激内源性组织特异性干细胞的扩增和功能,以增强组织再生。

 

迄今为止,在成体组织干细胞的再生潜力方面,我们所取得的进展已经超过了多能干细胞(PSC)的进展。在某些情况下,这些细胞(以下称为成体干细胞,也称为组织特异性干细胞)相对有限的潜能使其可能在细胞疗法方面具有超过ESC和iPSC的优势:我们较少担心这些细胞的致瘤性,并且这些细胞与ESC或iPSC来源的细胞类型相比,更有可能获得成体细胞典型的基因表达模式。递送“成体”干细胞的一种替代策略是发现靶向组织驻留原位成体干细胞的药物,以增强其再生功能。我们在本文中介绍了干细胞疗法开发中取得的进展和面临的挑战,重点是皮肤、心脏、眼睛、骨骼肌、神经组织、胰腺和血液。





作者信息

Helen M. Blau, Ph.D., and George Q. Daley, M.D., Ph.D.
From the Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA (H.M.B.); and the Department of Medicine, Harvard Medical School, Boston (G.Q.D.). Address reprint requests to Dr. Blau at Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Clinical Sciences Research Center, Rm. 4215, 269 Campus Dr., Stanford, CA 94305, or at hblau@stanford.edu.

 

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