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KMID : 0366220070420020106
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Korean Journal of Hematology
2007 Volume.42 No. 2 p.106 ~ p.113
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The Role of Bone Marrow Mononuclear Cells in Angiogenesis in Mouse Hind Limb Ischemic Model
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Cho Hyun-Min
Hong Jong-Wook
Kim Jun-Gi
Kim Jeong-A
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Abstract
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Background: Angiogenesis is enhanced in the ischemic tissues after the injection of bone marrow cells (BMCs). However the exact mechanisms for this are not yet fully understood.
Methods: A unilateral ischemic limb was surgically induced in mice and then BMCs were injected into the ischemic area. We measured the capillary/muscle ratio. Fluorescence-labeled BMCs were injected into the ischemic tissues and then the locations of the cells were examined by using a confocal microscope. Recruitment of bone marrow-derived cells into the ischemic tissue was examined in a sex-mismatched bone marrow transplantation (BMT) setting by identifying the Y chromosome with using the FISH technique. The expressions of VEGF, MMP-9, SDF-1 and CXCR-4 were measured by Western blot analysis.
Results: The capillary/muscle ratio was more increased in the BMC-injected group than in the control group (P＜0.05). Florescence-labeled BMCs, which had been directly injected into ischemic tissue, were not detected in the tissue. In the sex-mismatched bone marrow transplantation models, the ischemic tissues of the BMC-injected group recruited a much greater number of Y chromosome-positive bone marrow- derived cells, as compared to the control group. The expressions of VEGF and MMP-9 were increased after injection of BMCs. SDF-1 was expressed on the seventh day in the BMC-injected group and CXCR-4 was highly expressed until 12 weeks in the BMC-injected group.
Conclusion: We suggest that the injection of BMCs into ischemic tissue recruits CXCR-4-positvie cells from the bone marrow via the up-regulation of VEGF, MMP-9 and SDF-1, and these CXCR-4-positive cells may play a role in neovascularization. (Korean J Hematol 2007;42:106-113.)
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KEYWORD
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Ischemia, Angiogenesis, Bone marrow cell, VEGF, MMP-9, SDF-1, CXCR-4
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