期刊
CYTOTHERAPY
卷 15, 期 4, 页码 449-459出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2012.11.008
关键词
co-culture configuration; diabetes; islet culture; islet transplantation; mesenchymal stromal cells
类别
资金
- Biotechnology and Biological Sciences Research Council
- Novo Nordisk UK Research Foundation
- Diabetes UK [06/0003387, 11/0004290]
- Diabetes UK [11/0004290] Funding Source: researchfish
- Medical Research Council [985558] Funding Source: researchfish
Background aims. We recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplatit islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or beta-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome. Methods. The effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations. Results. Indirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo. Conclusions. Pre-culturing islets with MSCs using a direct contact configuration maintains functional beta-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice.
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