Formation of composite endothelial cell-mesenchymal stem cell islets: a novel approach to promote islet revascularization.
OBJECTIVE
Mesenchymal stem cells (MSCs) contribute to endothelial cell (EC) migration by producing proteases, thereby paving the way into the tissues for ECs. MSCs were added to our previously described composite EC islets as a potential means to improve their capacity for islet angiogenesis.


METHODS
Human islets were coated with primary human bone marrow-derived MSCs and dermal microvascular ECs. The capacity of ECs, with or without MSCs, to adhere to and grow into human islets was analyzed. The survival and functionality of these composite islets were evaluated in a dynamic perifusion assay, and their capacity for angiogenesis in vitro was assessed in a three-dimensional fibrin gel assay.


RESULTS
ECs proliferated after culture in MSC-conditioned medium, and MSCs improved the EC coverage threefold compared with EC islets alone. Islet survival in vitro and the functionality of the composite islets after culture were equal to those of control islets. The EC-MSC islets showed a twofold increase in total sprout formation compared with EC islets, and vascular sprouts emanating from the EC-MSC-islet surface showed migration of ECs into the islets and also into the surrounding matrix, either alone or in concert with MSCs.


CONCLUSIONS
EC proliferation, sprout formation, and ingrowth of ECs into the islets were enhanced by MSCs. The use of composite EC-MSC islets may have beneficial effects on revascularization and immune regulation. The technique presented allows for pretreatment of donor islets with recipient-derived ECs and MSCs as a means of improving islet engraftment.
Johansson
Ulrika
U
Division of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden. ulrika.johansson@klinimm.uu.se
Rasmusson
Ida
I
Niclou
Simone P
SP
Forslund
Naomi
N
Gustavsson
Linda
L
Nilsson
Bo
B
Korsgren
Olle
O
Magnusson
Peetra U
PU
D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D005109:Extracellular Matrix / Q000502:physiology; D005337:Fibrin; D005782:Gels; D006801:Humans; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
D005782:Gels; D005337:Fibrin