Intracoronary Infusion of Autologous CD133⁺ Cells in Myocardial Infarction and Tracing by Tc99m MIBI Scintigraphy of the Heart Areas Involved in Cell Homing

Abstract

CD133 mesenchymal cells were enriched using magnetic microbead anti-CD133 antibody from bone marrow mononuclear cells (BMMNCs). Flow cytometry and immunocytochemistry analysis using specific antibodies revealed that these cells were essentially 89 ± 4% CD133+ and 8 ± 5% CD34+. CD133+/CD34+ BMMNCs secrete important bioactive proteins such as cardiotrophin-1, angiogenic and neurogenic factors, morphogenetic proteins, and proinflammatory and remodeling factors in vitro. Single intracoronary infusions of autologous CD133+/CD34+ BMMNCs are effective and reduce infarct size in patients as analyzed by Tc99m MIBI myocardial scintigraphy. The majority of patients were treated via left coronary artery. Nine months after cell therapy, 5 out of 8 patients showed a net positive response to therapy in different regions of the heart. Uptake of Tc99 isotope and revitalization of the heart area in inferoseptal region are more pronounced (P = 0.016) as compared to apex and anterosptal regions after intracoronary injection of the stem cells. The cells chosen here have the properties essential for their potential use in cell therapy and their homing can be followed without major difficulty by the scintigraphy. The cell therapy proposed here is safe and should be practiced, as we found, in conjunction with scintigraphic observation of areas of heart which respond optimally to the infusion of autologous CD133+/CD34+ BMMNCs.

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial

“…On the contrary, Stamm et al [24] used CD133+ cells in the same group of patients and reported improved perfusion with a significant increase in LVEF at 3-year follow-up. Interestingly, intracoronary delivery of autologous BM-derived CD133+/CD34+ cells in patients with ischemic heart diseases and a history of MI (3-6 months before enrolment), proved to have a beneficial effect on myocardium by improving perfusion and reducing the scar area [25]. Furthermore, the clinical applicability of intracoronary delivered immune-selected cells was evaluated in patients with recent MI showing improved LV function [26,27].…”

Physiological Role of Bone Marrow Adult Stem Cell Cd133+

“…In an animal model (rat), two cell types, namely skeletal myoblasts or CD133 + progenitors led to improvement of cardiac function [14,15]. In human, we and other demonstrated that bone marrow CD133 + cells as a source of stem cell therapy can be used in several protocols for regenerative medicine (5). Here, we report that CD133 + cells isolated from bone marrow mononuclear cells, generates the spheroids and secrete a large array of regulatory proteins including several cytokines such as pro angiogenic factors, pro-inflammatory factors, matrix metalloproteinase and tissue inhibitor of metalloproteinases, neurophilic factors, morphogenetic proteins and hematopoietic growth factors.…”

“…Tissue regeneration may be due to infiltration of stem cells, which differentiate into other cells [1]. Laboratory experiments and recent clinical trials suggest that cell-based therapies can improve in several organ functions [2][3][4][5][6][7][8][9], and the implications of this for tissues regeneration are causing great excitement. These new findings have stimulated optimism that the progression regenerative medicine with cell-based therapy [4,6].…”

“…These new findings have stimulated optimism that the progression regenerative medicine with cell-based therapy [4,6]. Numerous studies have documented that transplantation of bone marrow derived cells following acute myocardial infarction and ischemic cardiomyopathy can lead to a reduction in infarct scar size and improvements in left ventricular function and perfusion [5]. Furthermore, the impact of successes may be affected by quality (progenitor source) and quantity of the cells, timing [10], route (intramuscular, intracoronary) and type of cardiomyopathy [11].…”

Selected CD133 + Progenitor Cells to Promote Angiogenesis in Patients With Refractory Angina

“…[17][18][19] In these studies the delivery method was the intracoronary injection or transmyocardial injection during surgery. To the best to our knowledge the current trial + surface marker is highly expressed on immature stem cell as it is downregulated as the cells differentiate to mature endothelial cell.…”