Institute for Systems Biology, Seattle, Washington, USA.
Physiol Genomics. 2009 Sep 9;39(1):72-81. doi: 10.1152/physiolgenomics.00063.2009. Epub 2009 Jul 21.
Pancreatic islet transplantation as a potential cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta-cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional beta-cells remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and for which redifferentiation was attempted. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at redifferentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increase our understanding of the active pathways in expanded and redifferentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta-cell mass in T1D patients.
胰岛移植作为治疗 1 型糖尿病（T1D）的一种潜在方法，由于人类胰腺供体稀缺，无法大规模推广。从成熟的人胰腺胰岛中体外扩增β细胞为产生胰岛素的细胞提供了另一种来源。不同的扩增方案所产生的扩增细胞的确切性质及其分化为功能性β细胞的潜力仍然难以捉摸。我们对人类胰岛细胞的基因表达进行了大规模的荟萃分析，这些细胞使用三种不同的先前描述的扩增方案进行处理，并且尝试了重新分化。所有三种扩增方案都诱导了胰岛表达谱的剧烈变化；这些变化中有许多是三种方案共有的。尝试对扩增细胞进行再分化会引起有限数量的基因表达变化。然而，这些变化并不能恢复胰岛样的基因表达模式。与一组公共微阵列数据集的比较证实，扩增细胞与间充质干细胞高度相似。在扩增细胞中诱导的基因也富集了对多能性诱导重要的转录因子的靶基因。目前的数据增加了我们对扩增和再分化胰岛中活跃途径的理解。了解间充质干细胞的潜力可能有助于开发药物治疗方法，以恢复 T1D 患者的β细胞质量。
