Human angiogenic cell precursors restore function in the infarcted rat heart: A comparison of cell delivery routes

Abstract

Background: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. Aims: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. Methods and results: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. Conclusions: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation.

Diagnostic and prognostic value of 3D NOGA mapping in ischemic heart disease

“…NOGA ® -guided injections of luciferase-transfected porcine mesenchymal stem cells showed significantly less washout of cells to remote organs than intracoronary infusion of the same cells. 74 However, in contrast to the cost and time of the NOGA ® -guided procedure, the intracoronary delivery mode is attractive in the clinical scenario owing to its simplicity and ease of use. The surgical delivery of regenerative substances, with or without bypass surgery (which cannot be performed in all territories owing to the presence of occluded arteries or poor run-off) has the advantage of visually guided intramyocardial delivery, allowing for high cell retention.…”

“…[11][12][13][14][15] Several experimental studies compared the different delivery platforms available for gene-based or cell-based therapy regarding efficiency and cell retention. 37,38,[71][72][73][74][75][76][77] The main differences between the intracoronary and intra myocardial delivery approaches have been summarized in original reports and reviews. 21,37,38,[71][72][73][74][75][76][77] Briefly, intra myocardial delivery demonstrated superior cell retention [72][73][74][75] without exposing the infarct-related artery to cell-sludge formation, 77 and had similar or higher efficacy as compared with intracoronary cell infusion.…”

Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor

“…Also, we delivered a considerable number of cardiomyocytes to infarcted myocardium that fused with the host cardiomyocytes, and integrated functionally with the recipient cardiac tissue. On the other hand, VEGF diminished cardiomyocyte apoptosis, stimulated cell proliferation, andmediated the migration of cardiac stem cells to infarcted myocardium post MI [30,42,43]. According to the above statements, we delivered and protected enough cardiomyocytes in ischemic hearts that hypothetically participated in cardiac regeneration, but the exact mechanism of how they function remains unclear yet.…”

Critical elements in the development of cell therapy potency assays for ischemic conditions

“…An array test showing that the cells secreted IL-8, VEGF and angiogenin was used to assess the product potency and later to narrow the range of tested cytokines to IL-8, which was subsequently used as a release test for the CTP [23]. Validation of the surrogate markerebased tests was achieved when the CTP was tested and shown to be effective in an in vivo rat model of ischemic cardiomyopathy [24] and in human patients with ischemic and non-ischemic cardiomyopathy [25,26] (Figure 3).…”