Bone marrow stem cells and islet co-transplantation promotes graft revascularization and function in small intestinal submucosa

E. Berishvili, Z. Kakabadze, I. Amiranashvili, K. Chutkerashvili
Tbilisi State Medical University, Tbilisi, Georgia

Objective: Type 1 diabetes is associated with aprogressive loss of beta cells and islet cell transplantation represents one ofthe most promising therapies. Recently we have shown that small intestinalsubmucosa is a sutable place for pancreatic islet transplantation. In thisstudy we show that transplantation of bone marrow cells into the smallintestinal submucosa allows minimal islet mass improve glycemic control in mousemodel.

Methods: Segments of small intestine were prepared by denudationof the mucosal layer prior to implantation. Streptozotocin induced diabetic C57Bl/6mice were transplanted syngeneically into the small intestinal submucosa withthe following: 100 islets alone (islet group: n = 12), 100 islets and 5 × 10⁶bone marrow cells (islet-bone marrow group: n = 12) and sham operated group nocells (sham group: n = 5). Blood glucose levels were monitored andintraperitoneal glucose tolerance tests carried out. Histological assessment forinsulin, glucagon, von Willebrand factor (vWF) was performed.

Results: Co-transplantation of 100 islets and 5 × 10⁶bone marrow cells reversed diabetes in all recipients, whereas islet-alonetransplantation achieved euglycemia in 2 of 12 recipients. Transplanted isletsdemonstrated expression of insulin and glucagon throughout the 90-day durationof the studies. Results of intravenous glucose tolerance tests performed on day56 were significantly better in islet-bone marrow group than islet-alonerecipients. One week after transplantation, well-preserved islet structure andhigher number of capillaries were found in the small intestinal segments ofislet- bone marrow recipients, whereas islet-alone grafts were fragmented withvery few capillaries. Removal of graft-bearing intestinal segments led torecurrence of hyperglycemia.

Conclusions: Islet co-transplantation with bone marrow isassociated with improvement of islet graft function.