Meivar-Levy Irit, Ferber Sarah
Sheba Medical Center, Endocrine Institute, Tel-Hashomer, Israel.
Methods Mol Biol. 2010;636:251-83. doi: 10.1007/978-1-60761-691-7_16.
Regenerative medicine aims at producing new cells for repair or replacement of diseased and damaged tissues. Embryonic and adult stem cells have been suggested as attractive sources of cells for generating the new cells needed. The leading dogma was that adult cells in mammals, once committed to a specific lineage, become "terminally differentiated" and can no longer change their fate. However, in recent years increasing evidence has accumulated demonstrating the remarkable ability of some differentiated cells to be converted into a different cell type via a process termed developmental redirection or adult cells reprogramming. For example, abundant human cell types, such as dermal fibroblasts and adipocytes, could potentially be harvested and converted into other, medically important cell types, such as neurons, cardiomyocytes, or pancreatic beta cells. In this chapter, we describe a method of activating the pancreatic lineage and beta-cells function in adult human liver cells by ectopic expression of pancreatic transcription factors. This approach aims to generate custom-made autologous surrogate beta cells for treatment of diabetes, and possibly bypass both the shortage of cadaveric human donor tissues and the need for life-long immune-suppression.
再生医学旨在制造新的细胞，用于修复或替换患病及受损组织。胚胎干细胞和成体干细胞被认为是生成所需新细胞的有吸引力的细胞来源。过去的主流观点认为，哺乳动物的成体细胞一旦确定了特定的细胞谱系，就会“终末分化”，不再能改变其命运。然而，近年来越来越多的证据表明，一些分化细胞具有显著的能力，能够通过一种称为发育重定向或成体细胞重编程的过程转化为另一种细胞类型。例如，大量的人类细胞类型，如皮肤成纤维细胞和脂肪细胞，有可能被获取并转化为其他医学上重要的细胞类型，如神经元、心肌细胞或胰腺β细胞。在本章中，我们描述了一种通过异位表达胰腺转录因子来激活成人肝细胞中胰腺谱系和β细胞功能的方法。这种方法旨在生成定制的自体替代β细胞用于治疗糖尿病，并有可能绕过尸体人类供体组织短缺以及终身免疫抑制的需求。
