| Project/Area Number |
16390366
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
GOTOH Mitsukazu Fukushima Medical University, Department of Surgery, Professor, 医学部, 教授 (50162160)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takuro Fukushima Medical University, Department of Surgery, Assistant, 医学部, 講師 (20305361)
KENJO Akira Fukushima Medical University, Department of Surgery, Assistant, 医学部, 助手 (40305355)
TSUCHIYA Takao Fukushima Medical University, Department of Surgery, Assistant, 医学部, 助手 (70343390)
TERASHIMA Masanori Fukushima Medical University, Department of Surgery, Associate Professor, 医学部, 助教授 (40197794)
佐藤 佳宏 福島県立医科大学, 医学部, 助手 (60347218)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2005: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Reconstitution of islets / Bone marrow cells / Composite graft / Streptozotocin / Partial pancreatectomy / GFP mice / 骨髄膵幹細胞 / PDX-1 |
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| Research Abstract |
Pancreatic islet transplantation to type I diabetes is currently undertaken for cure of the disease. However, one of problems to expand this program is a lack of tissue for transplantation. In this study, a possibility of bone marrow-derived cells for reconstitution or regeneration of pancreatic islets was investigated. Heterozygous GFP^+ (EGFP-transgenic line 15) mice of C57BL/6 (B6) background mice were used as source of marked bone marrow cells. Collagenase-digested B6 islets (150, 200-250, 300-350, 400-450 islets) were transplanted alone or together with 3 million of bone marrow cells of GFP mice into renal subcapsular space of streptozotocin-induced diabetic B6 mice. Animals were sacrificed to obtain specimen for immunohistochemical study using antibodies to detect insulin, glucagon, PDX-1, factor VIII, fibroblast specific protein(FSP). Blood glucose levels at early postoperative days tended to be higher when bone marrow cells were transplanted together with islets. Histologically, islet cells were dispersed and then reaggregated together to form a cell cluster like original pancreatic islets. During this procedure GFP positive bone marrow cells were demonstrated around islets to form a kind of cluster beside islets or to be integrated within islets. However, we failed to find bone marrow derived endocrine cells within the islets. Most of the GFP positive cells within islets appeared to be endothelial, dendritic, or fibroblastic cells. Interestingly, bone morrow cells in a cluster showed a typical phenotypic change similar to those in bone marrow. In another experiment inducing regeneration of islets by partial pancreatectomy or streptozotocin induced diabetes, bone marrow-derived cells were hardly integrated into pancreatic endocrine cells. However, traffic of bone marrow cells into regenerative tissue was enhanced before initiation of regeneration, suggesting a significant role of bone marrow cells for tissue regeneration.
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