| Project/Area Number |
18613019
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
NARUSE Keiko Aichi Gakuin University, School of Dentistry, Department of Internal Medicine, Associate Professor (30387576)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Tatsuaki Aichi Gakuin University, School of Dentistry, Department of Internal Medicine, Professor (30209598)
KOBAYASHI Yasuko Aichi Gakuin University, School of Dentistry, Department of Internal Medicine, Lecturer (40418926)
NAKAMURA Jiro Nagoya University, Graduate School of Medicine, Department of Endocrinology and Diabetes, Associate Professor (40283444)
SATO Jun Nagoya University, Research Institute of Environmental Medicine, Department of Neural Regulation, Associate Professor (00235350)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Diabetic neuropathy / Therapeutic vasculogenesis / Regenerative medicine / Bone marrow mononuclear cell |
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| Research Abstract |
Diabetic neuropathy is characterized by altered sensory excitability. The positive symptoms, including hyperalgesia, are often present in the early stage of diabetes. Since bone marrow is a rich source of not only vascular progenitor cells but also cytokines, we have examined whether the transplantation of bone marrow-derived MNCs into hindlimb muscles improves hyperalgesia observed in the early stage of STZ-induced diabetic rats.
Diabetes was induced by an intraperitoneal injection of STZ (60mg/Kg) into 6 week-old Sprague-Dawley rats. 2 weeks later, MNCs isolated from bone marrow or saline were injected into unilateral hindlimb skeletal muscles of diabetic rats. Behavioral nociceptive responses were measured every 2 or 3 days using von Frey hair. Two weeks after the injection of MNCs, sciatic nerve conduction velocity (NCV), and sciatic nerve blood flow (SNBF) were measured. mRNA expression of several cytokines in bone marrow-derived MNCs were examined using real time PCR. The frequenc
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y of paw withdrawal started to increase after STZ administration. The transplantation of MNCs significantly decreased the frequency of paw withdrawal in MNCs-injected side of diabetic rats compared with those in saline-injected side of diabetic rats. The effects of MNCs transplantation on hyperalgesia was observed from 3 days after MNCs transplantation until observation periods. Electrophysiological studies revealed that the trasnplantation of MNCs significantly ameliorated the impaired-NCV and SNBF in MNCs-injected side of diabetic rats compared with those in saline-injected side of diabetic rats. The mRNA expressions of the basic fibroblast growth factor and vascular endothelial growth factor were observed in MNCs.
These results indicate that bone marrow-derived MNCs is useful for not only therapeutic vasculogenesis but also a source of cytokines, suggesting that the transplantation of bone marrow-derived MNCs may be an effective therapy for hyperalgesia in the early stage of diabetes. Less
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