Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets.
OBJECTIVE
Long-term graft survival after islet transplantation to patients with type 1 diabetes is insufficient, necessitating the development of new strategies to enhance transplant viability. Here we investigated whether co-transplantation of neural crest stem cells (NCSCs) with islets improves islet survival and function in normoglycaemic and diabetic mice.


METHODS
Islets alone or together with NCSCs were transplanted under the kidney capsule to normoglycaemic or alloxan-induced diabetic mice. Grafts were analysed for size, proliferation, apoptosis and insulin release. In diabetic recipients blood glucose levels were examined before and after graft removal.


RESULTS
In mixed transplants NCSCs actively migrated and extensively associated with co-transplanted pancreatic islets. Proliferation of beta cells was markedly increased and transplants displayed improved insulin release in normoglycaemic mice compared with those receiving islet-alone transplants. Mixed grafts survived successfully and partially restored normoglycaemia in alloxan-induced diabetic mice.


CONCLUSIONS
Co-grafting of NCSCs with pancreatic islets improved insulin release in mixed transplants and enhanced beta cell proliferation, resulting in increased beta cell mass. This co-transplantation model offers an opportunity to restore neural-islet interactions and improve islet functions after transplantation.
Olerud
J
J
Department of Medical Cell Biology, Uppsala University Biomedical Center, Uppsala, Sweden.
Kanaykina
N
N
Vasylovska
S
S
Vasilovska
S
S
King
D
D
Sandberg
M
M
Jansson
L
L
Kozlova
E N
EN
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D017930:Genes, Reporter; D006085:Graft Survival / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D012016:Reference Values; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D001786:Blood Glucose; D049452:Green Fluorescent Proteins