Bone Marrow Cell Cotransplantation With Islets Improves Their Vascularization and Function

Background. To test the angiogenesis-promoting effects of bone marrow cells when cotransplanted with islets. Methods. Streptozotocin-induced diabetic BALB/c mice were transplanted syngeneically under the kidney capsule: (1) 200 islets, (2) 1 to 5 x 10(6) bone marrow cells, or (3) 200 islets and 1 to 5 x 10(6) bone marrow cells. All mice were evaluated for blood glucose, serum insulin, and glucose tolerance up to postoperative day (POD) 28, and a subset was monitored for 3 months after transplantation. Histologic assessment was performed at PODs 3, 7, 14, 28, and 84 for the detection of von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), insulin, cluster of differentiation-34, and pancreatic duodenal homeobox-1 (PDX-1) protein. Results. Blood glucose was the lowest and serum insulin was the highest in the islet + bone marrow group at POD 7. Blood glucose was significantly lower in the islet + bone marrow group relative to the islet only group after 63 days of transplantation (P < 0.05). Significantly more new periislet vessels were detected in the islet + bone marrow group compared with the islet group (P < 0.05). Vascular endothelial growth factor staining was more prominent in bone marrow than in islets (P < 0.05). Pancreatic duodenal homeobox-1-positive areas were identified in bone marrow cells with an increase in staining over time. However, there were no normoglycemic mice and no insulin-positive cells in the bone marrow alone group. Conclusions. Cotransplantation of bone marrow cells with islets is associated with enhanced islet graft vascularization and function.