Therapeutic actions of transcoronary sinus delivery of autologous bone marrow

JOSE VICARIO,; JULIO PIVA,; ANGEL PIERINI,; ORTEGA, HH; M CANAL, ANA; C GERARDO,; HERNAN PFEIFFER,; CESAR CAMPOS,

Stem Cell Research Advances

Nova Science Publishers

Lugar: New York; Año: 2007; p. 245 - 268

Ischemic coronary disease remains the leading cause of morbidity and mortality in the Western world. Current therapeutic approaches aim to relieve symptoms and cardiac events by reducing myocardial oxygen demand with medical therapy, to prevent further disease progression by modifying risk factors, or to restore flow to a localized segment of the arterial tree by coronary angioplasty (PTCA) or by coronary artery bypass grafting (CABG). Patients with severe myocardial ischemia who are not optimal candidates for percutaneous or surgical revascularization have few therapeutic options. In addition to symptoms that impair the quality of life, these patients are at risk of myocardial infarction and death. The natural process of collateral development, which can improve perfusion to jeopardized regions of myocardium, is inadequate in many patients [1-3]. This increasing clinical problem has stimulated interest in the use of angiogenesis growth factors to promote the growth of collateral blood vessels in ischemic tissues. Successful therapeutic angiogenesis has been demonstrated in a variety of species with a number of angiogenesis growth factors. [4-7] Despite multiple clinical study, efficacy of various angiogenesis strategies to improve myocardial perfusion remains unproven [8]. Given the complexity of natural angiogenesis processes, the delivery of a single angiogenesis factor, might provide a suboptimal stimulus to collateral development. Therefore, we tested a cell-based strategy based on the hypothesis that the cells secrete, in a time-and concentration-appropriate manner, multiple angiogenesis factors needed for optimal collateral development. Our preclinical studies [9] demonstrated that administration of autologous unfractionated bone marrow (AUBM) derived cells to ischemic porcine myocardium enhanced angiogenesis and that the coronary sinus as a route of administration was effective and well-tolerated. Presently, Phase I pilot and one-year follow-up studies designed to examine the effects of transcoronary sinus administration of autologous unfractioned bone marrow in patients with advanced coronary artery disease have demonstrated that this treatment is a safe, low risk and tolerable procedure. Preliminary results also show a significant improvement in the quality of life and the myocardial perfusion evaluated at one year. In this chapter, we will present our preclinical and clinical exprerience with enphasis on the coronary sinus as a route of administration of bone marrow-derived cells and the use of autologous unfractionated bone marrow as a biological agent.