Article

Diabetologia

, Volume 54, Issue 5, pp 1127-1135

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

  • C. L. RackhamAffiliated withDiabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King’s College London
  • , P. C. ChagastellesAffiliated withLaboratory of Immunogenetics, Department of Genetics, Universida de Federal do Rio Grande do Sul
  • , N. B. NardiAffiliated withLaboratory of Immunogenetics, Department of Genetics, Universida de Federal do Rio Grande do Sul
  • , A. C. Hauge-EvansAffiliated withDiabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King’s College London
  • , P. M. JonesAffiliated withDiabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King’s College London
  • , A. J. F. KingAffiliated withDiabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King’s College London Email author 

Abstract

Aims/hypothesis

Recent studies have shown that mesenchymal stem cells (MSCs) secrete several factors that improve survival and function of transplanted islets. Implantation of islets beneath the kidney capsule results in morphological changes, due to interactions of the graft with the host, thus impairing islet function. We co-transplanted MSCs with islets to determine their effects on the remodelling process and studied graft function in a mouse model of minimal islet mass.

Methods

Islets were syngeneically transplanted, either alone or with kidney-derived MSCs, underneath the kidney capsule of streptozotocin-induced diabetic C57Bl/6 mice. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests carried out. Hormone contents of grafts and pancreas were assessed by radioimmunoassay. Graft morphology and vascularisation were evaluated by immunohistochemistry.

Results

MSCs improved the capacity of islet grafts to reverse hyperglycaemia, with 92% of mice co-transplanted with MSCs reverting to normoglycaemia, compared with 42% of those transplanted with islets alone. Average blood glucose concentrations were lower throughout the 1 month monitoring period in MSC co-transplanted mice. MSCs did not alter graft hormone content. Islets co-transplanted with MSCs maintained a morphology that more closely resembled that of islets in the endogenous pancreas, both in terms of size, and of endocrine and endothelial cell distribution. Vascular engraftment was superior in MSC co-transplanted mice, as shown by increased endothelial cell numbers within the endocrine tissue.

Conclusions/interpretation

Co-transplantation of islets with MSCs had a profound impact on the remodelling process, maintaining islet organisation and improving islet revascularisation. MSCs also improved the capacity of islets to reverse hyperglycaemia.

Keywords

Diabetes Graft morphology Islet architecture Mesenchymal stem cells Transplantation