Sulzbacher Sabine, Schroeder Insa S, Truong Thuy T, Wobus Anna M
Leibniz Institute of Plant Genetics and Crop Plant Research, Corrensstr. 3, 06466 Gatersleben, Germany.
Stem Cell Rev Rep. 2009 Jun;5(2):159-73. doi: 10.1007/s12015-009-9061-5. Epub 2009 Mar 5.
The differentiation of murine and human embryonic stem (ES) cells into pancreatic cell types has been shown by several methods including spontaneous differentiation, formation of multi-lineage progenitors, lineage selection or transgene expression. However, these strategies led to a mixture of cells of all three primary germ layers and only a low percentage of definitive endoderm cells giving rise to pancreas, liver, lung and intestine. To reproducibly generate functional insulin-producing cells, ES cells have to be differentiated via definitive endoderm and pancreatic endocrine progenitors recapitulating the in vivo development. Activin A, a member of the transforming growth factor beta superfamily, has been shown to induce definitive endoderm cells dependent on concentration, culture conditions and time of application. Moreover, serum components or contamination by feeder cells as well as differentiation and proliferation factors are critical for successful generation of activin A-induced ES cells into endoderm and pancreatic cells. The review presents an overview on those factors that influence activin A activity on endoderm and endocrine progenitor cells and determines the role of signaling factors in the differentiation process into the pancreatic lineage.
包括自发分化、多谱系祖细胞形成、谱系选择或转基因表达在内的多种方法已证明，小鼠和人类胚胎干细胞可分化为胰腺细胞类型。然而，这些策略会导致所有三个原始胚层的细胞混合，只有低比例的定形内胚层细胞可分化为胰腺、肝脏、肺和肠道。为了可重复地生成功能性胰岛素产生细胞，胚胎干细胞必须通过定形内胚层和胰腺内分泌祖细胞进行分化，以重现体内发育过程。激活素A是转化生长因子β超家族的成员，已证明其可根据浓度、培养条件和应用时间诱导定形内胚层细胞。此外，血清成分、饲养细胞污染以及分化和增殖因子对于激活素A诱导的胚胎干细胞成功分化为内胚层和胰腺细胞至关重要。本文综述了影响激活素A对内胚层和内分泌祖细胞活性的因素，并确定了信号因子在胰腺谱系分化过程中的作用。
