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

Diabetologia. 2009 Dec;52(12):2594-601. doi: 10.1007/s00125-009-1544-z. Epub 2009 Oct 13.


Aims/hypothesis: 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/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cell Division
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / surgery*
  • Genes, Reporter
  • Graft Survival / physiology
  • Green Fluorescent Proteins / genetics
  • Insulin-Secreting Cells / cytology*
  • Islets of Langerhans / physiology*
  • Islets of Langerhans Transplantation / methods
  • Islets of Langerhans Transplantation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Crest / cytology*
  • Neural Crest / physiology
  • Neural Crest / transplantation*
  • Reference Values
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology
  • Stem Cells / physiology*


  • Blood Glucose
  • Green Fluorescent Proteins