THERAPEUTIC ANGIOGENESIS BY BONE MARROW MONONUCLEAR CELL TRANSPLANTATION AND QUANTITATIVE EVALUATION OF ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH PERIPHERAL OBSTRUCTIVE ARTERIAL DISEASE

Abstract

We performed therapeutic angiogenesis by cell transplantation (TACT) for patients with peripheral obstructive arterial disease using autologous bone marrow mononuclear cells. The patients' symptom has begun to improve within several days after therapy, as did laboratory data (i. e., anklebrachial blood pressure index, thermography, percutaneous measurement of oxygen pressure). We quantified the mRNA expression of endothelial progenitor cell (EPC) -specific molecules (e. g., Flk-1, CD133, VE-cadherin, etc.) in bone marrow- or peripheral blood-derived mononuclear cells obtained from patients with ischemic limbs, using real time reverse transcription-PCR. The mRNA expression level of EPC markers was significantly lower in the patients than in healthy controls. We furthermore revealed the different expression pattern of EPC markers in several sources, including bone marrow and peripheral blood obtained from healthy volunteers or recombinant G-CSF-treated donors. The finding that the expression of EPC-specific molecules was decreased in the patients' marrow and blood suggests that patients with peripheral obstructive arterial diseases may have lower angiogenic potential. However, TACT with autologous marrow mononuclear cells was effective and increased the number of circulating EPCs in the patients' blood.