Liew Chee-Gee
UCR Stem Cell Center, University of California, Riverside, CA 92521, USA.
Rev Diabet Stud. 2010 Summer;7(2):82-92. doi: 10.1900/RDS.2010.7.82. Epub 2010 Aug 10.
The pancreas arises from Pdx1-expressing progenitors in developing foregut endoderm in early embryo. Expression of Ngn3 and NeuroD1 commits the cells to form endocrine pancreas, and to differentiate into subsets of cells that constitute islets of Langerhans. β-cells in the islets transcribe gene-encoding insulin, and subsequently process and secrete insulin, in response to circulating glucose. Dysfunction of β-cells has profound metabolic consequences leading to hyperglycemia and diabetes mellitus. β-cells are destroyed via autoimmune reaction in type 1 diabetes (T1D). Type 2 diabetes (T2D), characterized by impaired β-cell functions and reduced insulin sensitivity, accounts for 90% of all diabetic patients. Islet transplantation is a promising treatment for T1D. Pluripotent stem cells provide an unlimited cell source to generate new β-cells for patients with T1D. Furthermore, derivation of induced pluripotent stem cells (iPSCs) from patients captures "disease-in-a-dish" for autologous cell replacement therapy, disease modeling, and drug screening for both types of diabetes. This review highlights essential steps in pancreas development, and potential stem cell applications in cell regeneration therapy for diabetes mellitus.
胰腺起源于胚胎早期发育中的前肠内胚层中表达Pdx1的祖细胞。Ngn3和NeuroD1的表达使细胞定向形成内分泌胰腺，并分化为构成胰岛的细胞亚群。胰岛中的β细胞转录编码胰岛素的基因，随后响应循环葡萄糖加工并分泌胰岛素。β细胞功能障碍会导致严重的代谢后果，进而引发高血糖和糖尿病。在1型糖尿病（T1D）中，β细胞通过自身免疫反应被破坏。2型糖尿病（T2D）的特征是β细胞功能受损和胰岛素敏感性降低，占所有糖尿病患者的90%。胰岛移植是治疗T1D的一种有前景的方法。多能干细胞为T1D患者提供了产生新β细胞的无限细胞来源。此外，从患者体内获得诱导多能干细胞（iPSC）可用于“培养皿中的疾病”研究，用于自体细胞替代治疗、疾病建模以及两种糖尿病的药物筛选。本综述重点介绍了胰腺发育的关键步骤，以及干细胞在糖尿病细胞再生治疗中的潜在应用。
