Bone marrow (BM) transplantation promotes beta-cell regeneration after acute injury through BM cell mobilization

Endocrinology. 2007 May;148(5):2006-15. doi: 10.1210/en.2006-1351. Epub 2007 Jan 25.


There is controversy regarding the roles of bone marrow (BM)-derived cells in pancreatic beta-cell regeneration. To examine these roles in vivo, mice were treated with streptozotocin (STZ), followed by bone marrow transplantation (BMT; lethal irradiation and subsequent BM cell infusion) from green fluorescence protein transgenic mice. BMT improved STZ-induced hyperglycemia, nearly normalizing glucose levels, with partially restored pancreatic islet number and size, whereas simple BM cell infusion without preirradiation had no effects. In post-BMT mice, most islets were located near pancreatic ducts and substantial numbers of bromodeoxyuridine-positive cells were detected in islets and ducts. Importantly, green fluorescence protein-positive, i.e. BM-derived, cells were detected around islets and were CD45 positive but not insulin positive. Then to examine whether BM-derived cell mobilization contributes to this process, we used Nos3(-/-) mice as a model of impaired BM-derived cell mobilization. In streptozotocin-treated Nos3(-/-) mice, the effects of BMT on blood glucose, islet number, bromodeoxyuridine-positive cells in islets, and CD45-positive cells around islets were much smaller than those in streptozotocin-treated Nos3(+/+) controls. A series of BMT experiments using Nos3(+/+) and Nos3(-/-) mice showed hyperglycemia-improving effects of BMT to correlate inversely with the severity of myelosuppression and delay of peripheral white blood cell recovery. Thus, mobilization of BM-derived cells is critical for BMT-induced beta-cell regeneration after injury. The present results suggest that homing of donor BM-derived cells in BM and subsequent mobilization into the injured periphery are required for BMT-induced regeneration of recipient pancreatic beta-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bone Marrow Transplantation*
  • Cell Count
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / therapy*
  • Female
  • Hematopoietic Stem Cell Mobilization*
  • Hyperglycemia / pathology
  • Hyperglycemia / therapy
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / physiology
  • Leukocyte Common Antigens / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type III
  • Pancreatic Ducts
  • Regeneration
  • Whole-Body Irradiation


  • Insulin
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Leukocyte Common Antigens
  • Ptprc protein, mouse