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 5x10 bone marrow cells, or (3) 200 islets and 1 to 5x10 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.
Sakata
Naoaki
N
Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, CA, USA.
Chan
Nathaniel K
NK
Chrisler
John
J
Obenaus
Andre
A
Hathout
Eba
E
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D042501:Angiogenic Proteins; D018952:Antigens, CD34; D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; C084010:pancreatic and duodenal homeobox 1 protein; C467480:vascular endothelial growth factor A, mouse; D014841:von Willebrand Factor