Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets

• AIMS/HYPOTHESIS: Long-term graft survival after islet transplantation to patientswith type 1 diabetes is insufficient, necessitating the development of newstrategies to enhance transplant viability. Here we investigated whetherco-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 tonormoglycaemic or alloxan-induced diabetic mice. Grafts were analysed for size,proliferation, apoptosis and insulin release. In diabetic recipients bloodglucose levels were examined before and after graft removal. RESULTS: In mixedtransplants NCSCs actively migrated and extensively associated withco-transplanted pancreatic islets. Proliferation of beta cells was markedlyincreased and transplants displayed improved insulin release in normoglycaemicmice compared with those receiving islet-alone transplants. Mixed grafts survivedsuccessfully and partially restored normoglycaemia in alloxan-induced diabeticmice. CONCLUSIONS/INTERPRETATION: Co-grafting of NCSCs with pancreatic isletsimproved insulin release in mixed transplants and enhanced beta cellproliferation, resulting in increased beta cell mass. This co-transplantationmodel offers an opportunity to restore neural-islet interactions and improveislet functions after transplantation.

Nyckelord

Diabetes

Islets of Langerhans

Neural stem cells

Transplantation

Trophic factor

MEDICINE

MEDICIN

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