Intrapericardial Administration of Mesenchymal Stem Cells in a Large Animal Model: A Bio-Distribution Analysis

Abstract

The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

Myocardial homing of mesenchymal stem cells following intrapericardial application and amplification by inflammation — an experimental pilot study

“…However, the feasibility of the concept is in line with other recent studies, in which myocardial homing of intrapericardially applied stem cells was shown (Blázquez et al 2015(Blázquez et al , 2016Branco et al 2009). Further studies are required to investigate the detailed pathway of stem cell homing; there is evidence that inflammation could play an essential role (Zhang et al 2016).…”

“…To our best knowledge, this is the first study reporting effects of inflammation in terms of a sterile pericarditis on increased myocardial homing. MSC viability, the proliferative behavior and phenotypic pattern, appears unaffected by exposure to pericardial fluid as previously shown (Blázquez et al 2015). Pericardial fluid with a low turnover rate has the potential to serve as therapeutic depot, which allows delivery of high doses of MSCs into pericardial sac.…”

“…In addition, it is known that drugs applied into the pericardial space can penetrate the myocardium (Marcano et al 2013). There are yet only very few studies on myocardial homing of stem cells after intrapericardial administration (Blázquez et al 2015(Blázquez et al , 2016Branco et al 2009). None of them considered amplifying effects of local inflammation.…”

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…121 Also using a very large number (100×10 6 ) of SPION-labeled mesenchymal stem cells delivered by intrapericardial administration in porcine models, the authors identified a significant number of cells retained in the cardiac tissue a few days after injection. 122 In small rodents, it was possible to observe SPION-labeled mesenchymal stem cells (Endorem) after direct injection into the myocardial infarction scar. 123 In our experiments, we also were able to detect SPION-labeled mesenchymal cells after injection of 3×10 6 cells into leg muscle of mice, 15,24 1×10 6 cells into rat striatum, 124 and 5×10 6 rat intravitreally.…”

Optical fluorescence imaging with shortwave infrared light emitter nanomaterials for in vivo cell tracking in regenerative medicine

“…Local injection in the parenchyma is an invasive method and may lead to further damage to the target tissue . Direct intramyocardial cell delivery developed cardiac arrhythmias and had deteriorating effect on the heart …”