Gershengorn Marvin C, Geras-Raaka Elizabeth, Hardikar Anandwardhan A, Raaka Bruce M
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-8029, USA.
Cell Cycle. 2005 Mar;4(3):380-2. doi: 10.4161/cc.4.3.1538. Epub 2005 Mar 17.
To generate cells for replacement therapy for patients with diabetes, preclinical research is being conducted to establish in vitro systems that generate large numbers of human islets of Langerhans (or insulin-expressing beta cells). Based on the concept that undifferentiated precursor cells can expand exponentially and then be induced to differentiate into mature cells, researchers are using islet (or beta cell) precursor cells for this purpose. The cells being used include embryonic stem cells, bone marrow-derived stem cells, pancreatic stem cells and cells derived from epithelial-to-mesenchymal transition of insulin-expressing cells. Transdifferentiation of another epithelial cell type is being studied also. Herein, we review our data of epithelial-to-mesenchymal-to-epithelial transition of human insulin-expressing cells and present our hypothesis that precursor cells obtained from insulin-expressing cells by epithelial-to-mesenchymal transition, after expansion, more easily differentiate into insulin-expressing cells (by mesenchymal-to-epithelial transition) than other precursor cells or by transdifferentiation.
为了生成用于糖尿病患者替代疗法的细胞,正在进行临床前研究以建立能够大量生成人类胰岛(或表达胰岛素的β细胞)的体外系统。基于未分化前体细胞可以指数级扩增然后被诱导分化为成熟细胞的概念,研究人员正为此使用胰岛(或β细胞)前体细胞。所使用的细胞包括胚胎干细胞、骨髓来源的干细胞、胰腺干细胞以及由表达胰岛素细胞的上皮-间充质转化衍生而来的细胞。另一种上皮细胞类型的转分化也在研究中。在此,我们回顾我们关于人类表达胰岛素细胞的上皮-间充质-上皮转化的数据,并提出我们的假设,即通过上皮-间充质转化从表达胰岛素细胞获得的前体细胞,在扩增后,比其他前体细胞或通过转分化更容易分化为表达胰岛素的细胞(通过间充质-上皮转化)。