Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets.
OBJECTIVE
To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.


METHODS
Streptozotocin induced diabetic BALB/c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n = 12), (2) 1-5 x 10(6) bone marrow cells (bone marrow group: n = 11), (3) 200 islets and 1-5 x 10(6) bone marrow cells (islet + bone marrow group: n = 13), or (4) no cells (sham group: n = 5). All mice were evaluated for blood glucose, serum insulin, serum nerve growth factor (NGF) and glucose tolerance (GTT) up to postoperative day (POD) 14. Histological assessment for insulin, von Willebrand factor (vWF) and NGF was performed at POD 3, 7 and 14.


RESULTS
Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P = 0.0496, ANOVA) between the bone marrow and sham groups. The number of vessels within the graft area was significantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 +/- 3.6 in bone marrow, P = 0.01, vs islet group, 22.6 +/- 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 +/- 1.6 in islet-alone transplants). NGF was more strongly expressed in bone marrow cells compared with islets.


CONCLUSIONS
Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.
Sakata
Naoaki
N
Division of Pediatric Endocrinology, Pediatric Diabetes Center and Islet Transplant Laboratory, Department of Pediatrics, Loma Linda University School of Medicine, 11175 Campus Street, Coleman Pavilion, A1120R, Loma Linda, CA 92354, United States.
Chan
Nathaniel-K
NK
Chrisler
John
J
Obenaus
Andre
A
Hathout
Eba
E
D000818:Animals; D001786:Blood Glucose; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D020932:Nerve Growth Factor / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D020932:Nerve Growth Factor