Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Mar 14, 2010; 16(10): 1215-1220
Published online Mar 14, 2010. doi: 10.3748/wjg.v16.i10.1215
Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets
Naoaki Sakata, Nathaniel K Chan, John Chrisler, Andre Obenaus, Eba Hathout
Naoaki Sakata, Nathaniel K Chan, John Chrisler, Eba Hathout, Islet Transplant Laboratory, Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA 92354, United States
Naoaki Sakata, Division of Hepato-Biliary Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Andre Obenaus, Departments of Radiation Medicine and Radiology, Loma Linda University School of Medicine, Loma Linda, CA 92354, United States
Author contributions: Sakata N designed and performed the study, and wrote the initial draft of the manuscript; Chan NK and Obenaus A assisted in writing the draft; Chrisler J performed animal surgery; Hathout E helped with the design, supervised data collection, and wrote the final version of the manuscript.
Supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) Grant # 1R01-DK077541 (to Hathout E) and a grant from the National Medical Test Bed (to Hathout E)
Correspondence to: Eba Hathout, MD, Professor, Chief, Director, 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. ehathout@llu.edu
Telephone: +1-909-5584773  Fax: +1-909-5580479
Received: November 26, 2009
Revised: January 5, 2010
Accepted: January 12, 2010
Published online: March 14, 2010
Abstract

AIM: 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 × 106 bone marrow cells (bone marrow group: n = 11), (3) 200 islets and 1-5 × 106 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.

CONCLUSION: Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.

Keywords: Islet transplantation, Bone marrow cells, Nerve growth factor, Angiogenesis, Endothelial precursor cells