Therapy And Its Underlying Mechanisms Of Bone Marrow Stem Cell Mobilization For Acute Limb Ischemia In A Mice Model

A new therapy appears to cure limb ischemic diseases, such as PAOD(Peripheral arterial occlusive disease), by promoting neovascularization to ameliorate tissue ischemia. Recent studies show that vascular endothelium is differentiated from bone marrow stem cell, and ischemia of limb muscle tissue gives rise to peripheral blood stem cells. These discoveries promoted us to bring out such a question: could it be possible to increase neovascularization by bone marrow stem cell mobilization. To test this possibility , we investigated mice hindlimb ischemic models, observing the effects of bone marrow mobilization in peripheral blood, examining pathological and immuno-pathological changes in the ischemic muscle tissue .Subjects and methods :â‘ Mice hindlimb ischemic models was made by right FA (Femoral arterial) ligation, and then was given injections of GM-CSF successively for 7days. The control group was given injections of saline. â‘¡Peripheral blood WBC and CD34⁺ cells were counted in day 1 (before FA ligation) and day 8 by Flow Cytometry. (3) 8 days after right FA ligation, mice hind limb muscle were excised to make pathological sections, vessel number were counted in mobilized or non-mobilized group by Immunohistochemistry study with Factor â…§ multi-cloned antibody. Results :?WBC and CD34+ cells in peripheral blood of hindlimb ischemic mice were increased significantly in day 8 after right FA was ligated . Compared with non-mobilized group, WBC and CD34⁺ cells in mobilizedgroup increased much more , the maximum difference reached 10 fold. â‘¡ Immunohistochemistry study showed that vessels stained with Factor â…§ multi-cloned Ab in mobilized group is 1.52 time more than the non-mobilized group.Conclusions: â‘ After hindlimb ischimia in a mice model, peripheral blood stem cell were mobilized from bone marrow, and CD34⁺ cells in peripheral blood were increased significantly. â‘¡ GM-CSF ,one of bone marrow stem cell mobilizers, can amplify mobilization in this ischemia setting. (3)Bone marrow stem cell mobilization increases vascular density in the ischemic muscle tissues, and improve the function of the ischemic hindlimb.