Limited Capacity of Human Adult Islets Expanded In Vitro to Redifferentiate Into Insulin-Producing B-Cells

*KAYALI AG; *FLORES LE; KUTLU B; BAETGE E; KITAMURA R; HAO E; BEATTIE GM; HAYEK A; * KAG Y LEF CONTRIBUYERON DE IGUAL MANERA AL TRABAJO

DIABETES

American Diabetes Association

Lugar: Baltimore; Año: 2007 vol. 56 p. 703 - 708

0012-1797

Limited organ availability is an obstacle to the widespread use of islet transplantation in type 1 diabetic patients. To address this problem, many studies have explored methods for expanding functional human islets in vitro for diabetes cell therapy. We previously showed that islet cells replicate after monolayer formation under the influence of hepatocyte growth factor and selected extracellular matrices. However, under these conditions, senescence and loss of insulin expression occur after >15 doublings. In contrast, other groups have reported that islet cells expanded in monolayers for months progressed through a reversible epithelial-to-mesenchymal transition, and that on removal of serum from the cultures, islet-like structures producing insulin were formed (1). The aim of the current study was to compare the two methods for islet expansion using immunostaining, real-time quantitative PCR, and microarrays at the following time points: on arrival, after monolayer expansion, and after 1 week in serum-free media. At this time, cell aliquots were grafted into nude mice to study in vivo function. The two methods showed similar results in islet cell expansion. Attempts at cell dif differentiation ferentiation after expansion by both methods failed to consistently recover a B-cell -phenotype. Redifferentiation of B-cells -after expansion is still a challenge in need of a solution.