Preparatory studies of composite mesenchymal stem cell islets for application in intraportal islet transplantation.
BACKGROUND
Low engraftment and adverse immune reactions hamper the success rate of clinical islet transplantation. In this study, we investigated the capacity of human mesenchymal stem cells (MSCs) to adhere to human islets of Langerhans and their effects in immune modulation and during blood interactions in vitro.


METHODS
Composite MSC-islets were formed by suspension co-culture, and the phenotype was evaluated by confocal microscopy. Islet function was assessed by dynamic insulin release in response to glucose in vitro. Mixed lymphocyte-islet reactions (MLIR) and the tubing blood loop model were utilized as in vitro tools to analyse the effect of MSCs on the innate and adaptive immune reactions triggered by the islets.


RESULTS
MSCs rapidly adhered to islets and spread out to cover the islet surface. Insulin expression and secretion were sustained with the MSC coating. MSC-coated islets showed unaffected reactions with blood in vitro in comparison to control islets. Furthermore, MSCs suppressed lymphocyte proliferation induced by islet cells in MLIR.


CONCLUSIONS
We conclude that it is possible to create composite MSC-islets to enable delivery of the MSCs by utilizing the adhesive capacity of the MSCs. This could have beneficial immunosuppressive effects in optimizing pancreatic islet transplantation.
Uppsala University, Department of Oncology, Radiology and Clinical Immunology, Division of Clinical Immunology, The Rudbeck Laboratory, Uppsala, Sweden.
Ida Rasmusson
IR
Duprez
Ulrika
U
Johansson
Bo
B
Nilsson
Olle
O
Korsgren
Peetra U
PU
Magnusson
D000818:Animals; D002448:Cell Adhesion; D018920:Coculture Techniques; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL
D007328:Insulin