Ouziel-Yahalom Limor, Zalzman Michal, Anker-Kitai Leeat, Knoller Sarah, Bar Yael, Glandt Mariela, Herold Kevan, Efrat Shimon
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Biochem Biophys Res Commun. 2006 Mar 10;341(2):291-8. doi: 10.1016/j.bbrc.2005.12.187. Epub 2006 Jan 19.
Beta-cell replacement represents the ultimate cure for type 1 diabetes, however it is limited by availability of organ donors. Adult human islets are difficult to propagate in culture, and efforts to expand them result in dedifferentiation. Here we describe conditions for expansion of adult human islet cells, as well as a way for their redifferentiation. Most cells in islets isolated from human pancreata were induced to replicate within the first week of culture in expansion medium. Cells were propagated for 16 population doublings, without a change in replication rate or noticeable cell mortality, representing an expansion of over 65,000-fold. Replication was accompanied by a decrease in expression of key beta-cell genes. Shift of the cells to differentiation medium containing betacellulin resulted in redifferentiation, as manifested by restoration of beta-cell gene expression and insulin content. These methods may allow transplantation of functional islet cells from single donors into multiple recipients.
β细胞替代是1型糖尿病的终极治疗方法，然而它受到器官供体可用性的限制。成人胰岛在培养中难以增殖，并且扩大它们的努力会导致去分化。在这里，我们描述了成人胰岛细胞的扩增条件以及它们重新分化的方法。从人胰腺分离的胰岛中的大多数细胞在扩增培养基中培养的第一周内被诱导复制。细胞增殖了16次群体倍增，复制速率没有变化，细胞死亡率也不明显，这意味着扩增超过65000倍。复制伴随着关键β细胞基因表达的下降。将细胞转移到含有β细胞素的分化培养基中会导致重新分化，表现为β细胞基因表达和胰岛素含量的恢复。这些方法可能允许将来自单个供体的功能性胰岛细胞移植到多个受体中。
