Peripheral Blood Autologous CD34+ Cell Transplantation Promotes Angiogenesis in Elderly Patients With Atherosclerotic Ischemia: Study Protocol for a Prospective, Single-center, Open-label, Randomized, Controlled, Clinical Trial

History and current related studies Arteriosclerosis obliterans is a kind of arterial lumen stenosis and occlusive disease, which is caused by the continuous expansion of arterial atherosclerosis and secondary thrombosis. Clinical manifestations are local skin temperature reduction, intermittent claudication, rest pain, ulcers difficult to heal, and gangrene infection.Some patients require amputation or even it is life-threatening. Arteriosclerosis obliterans of lower limbs are commonly treated by surgical treatment, endovascular treatment and non-surgical treatment, but the effect is not very satisfactory.

For the treatment of arteriosclerosis obliterans, stem cell transplantation has achieved great progress in angiogenesis and collateral circulation. There are two main mechanisms of stem cells involved in angiogenesis: (1) Promoting differentiation and maturation of new blood vessels by homing and integration in the damaged vascular plexus; (2) Promoting angiogenesis in ischemic tissue by paracrine of vascular endothelial growth factor (VEGF).In recent years, because of the discovery of endothelial progenitor cells in peripheral blood, the concept of angiogenesis has been renewed. Transplantation of endothelial progenitor cells and bone marrow cells for angiogenesis has become the focus of research. Endothelial progenitor cell and bone marrow cell transplantation have been used to promote angiogenesis in ischemic tissue in order to treat limb ischemia.

Bone marrow stem cell mobilization is used to promote the replication of bone marrow stem cells, so as to increase the number of endothelial progenitor cells in peripheral blood, i.e., the number of stem cells homing to ischemic tissue, and finally accelerating the speed and magnitude of angiogenesis. Fujisaki et al. have confirmed that bone marrow cell mobilizers can significantly stimulate bone marrow hematopoiesis and increase the number of peripheral blood stem cells.Bone marrow cell mobilizer-recombinant human granulocyte colony stimulating factor (rhG-CSF) are used to mobilize bone marrow stem cells to peripheral blood, and to increase the number of peripheral blood stem cells, especially endothelial progenitor cells, so as to treat ischemic diseases using transplanted autologous stem cells, which is called autologous stem cell transplantation. Nevertheless, in animal and human experiments, the proliferation potential and influencing factors of mobilized bone marrow stem cells and peripheral blood endothelial progenitor cells in ischemic tissue require further investigations.

Autologous stem cell transplantation is to transplant stem cells in muscles of ischemic limb, so that new capillaries improve and restore lower limb blood flow, aiming to treat lower limb ischemia. Endothelial progenitor cells and hematopoietic stem cells are thought to come from a common ancestor, and called blood vessel stem cells. They express immature stem cell markers CD34 and CD133. Endothelial progenitor cells migrated from bone marrow to peripheral blood will gradually lose CD133, and the disappearance of CD34 is relatively slow. A large number of basic and clinical studies have confirmed that the transplantation of CD34+ cells can promote angiogenesis in ischemic limbs of experimental animals (partial patients).

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