Transplantation of CD34+ cells for myocardial ischemia

Abstract

CD34+ cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine. Naturally, these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury. CD34+ cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage. They have an important paracrine activity in secreting factors to stimulate vasculogenesis, reduce endothelial cells and cardiomyocytes apoptosis, remodel extracellular matrix and activate additional progenitor cells. Once they migrate to the target site, they enhance angiogenesis, neovascularization and tissue regeneration. Several trials have demonstrated the safety and efficacy of CD34+ cell therapy in different settings, such as peripheral limb ischemia, stroke and cardiovascular disease. Herein, we review the potential utility of CD34+ cell transplantation in acute myocardial infarction, refractory angina and ischemic heart failure.

Keywords: Cell therapy; Coronary microvascular dysfunction; Endothelial progenitor cells; Heart failure; Myocardial ischemia; Refractory angina.

Figure 1

Role of CD34+ cells in ischemic myocardial repair. A: In response to ischemic injury, several factors like granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, interleukin (IL)-3, IL-8, IL-11, cysteine-rich angiogenic protein 61 (CCN1) and integrin antibodies (Antiα4β1) trigger mobilization of CD34+ cells from the bone marrow into peripheral circulation; B: Mechanisms of action of CD34+ cells on cardiomyocytes via paracrine activity are transdifferentiation into smooth muscle and endothelial cells, neovascularization, matrix remodeling, reduced apoptosis and recruitment of additional stem/progenitor cells; C: The main cardiovascular outcomes of CD34+ cells. G-CSF: Granulocyte colony stimulating factor; GM-CSF: Granulocyte macrophage colony stimulating factor; IL: Interleukin; CCN1: Cysteine-rich angiogenic protein 61.