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

Abstract

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.

• Authors: Yutaka Hasegawa, Takehide Ogihara, Tetsuya Yamada, Yasushi Ishigaki, Junta Imai, Kenji Uno, Junhong Gao, Keizo Kaneko, Hisamitsu Ishihara, Hironobu Sasano, Hiromitsu Nakauchi, Yoshitomo Oka, Hideki Katagiri
• Journal: Endocrinology (Endocrinology) Vol. 148 Issue 5 Pg. 2006-15 (May 2007) ISSN: 0013-7227 [Print] United States
• PMID: 17255204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acute Disease
• Animals
• Bone Marrow Transplantation
• Cell Count
• Diabetes Mellitus, Experimental (pathology, therapy)
• Female
• Hematopoietic Stem Cell Mobilization
• Hyperglycemia (pathology, therapy)
• Insulin (metabolism)
• Insulin-Secreting Cells (cytology, 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