Radiolabeled Cell Distribution After Intramyocardial, Intracoronary, and Interstitial Retrograde Coronary Venous Delivery

Abstract

Background— Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results— Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10 7 111 indium-oxine–labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3% (IM), 47±1% (IC), and 43±3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3%) compared with IC (2.6±0.3%) ( P <0.05) delivery. IRV delivery efficiency (3.2±1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions— The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Proteomic Analysis of Estrogen-Mediated Enhancement of Mesenchymal Stem Cell-Induced Angiogenesis In Vivo

“…Consequently, MSCs have become the cell of choice for therapeutic use in tissue repair [5]. However, a review of studies conducted in the last two decades suggests that a limiting factor for MSC-based therapy is the engraftment of low number of MSCs (0.44-1%) [3,10] in damaged sites and lack of understanding of the mechanisms involved in MSCs engraftment [11]. There is a consensus that strategies that would improve MSCs homing and engraftment are required to optimize their therapeutic use.…”

“…Although attractive, a major limitation of MSCs therapy is the low engraftment yield of transplanted cells in infarcted zones; approximately only 0.44% of transplanted MSCs reside in the myocardium after 4 days [3,10]. Moreover, direct intra-cardiac delivery of MSCs does not substantively increase their engraftment yield (range 1-3%) [11]. Clearly, a better understanding of MSCs biology is required to optimize MSCs therapy [12].…”

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction

“…The cardiac patch developed requires open-heart surgery to implant the patch, either by suturing [164,165] or by applying bioglue to the patch [166]. A PCL/gelatin patch incorporated with MSCs activated endogenous cardiac repair by enhancing the survival of MSCs and their HIF-1a, Tb4, VEGF, and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions.…”

Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration

“…For example, early studies in an ischemic swine model demonstrated retention rates of peripheral blood mononuclear cells within the myocardium of only about 2.6%, 3.2%, and 11% after intracoronary, interstitial retrograde coronary venous, and intramyocardial delivery, respectively [127]. For these low retention rates, some of the delivery routes are controversially discussed regarding their actual impact on the recovery of cardiac function [126,128].…”