Abstract
BackgroundMesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status.ObjectivesTo examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance.MethodsHealthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups.ResultsCFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted.ConclusionOverall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.
Highlights
Cardiovascular diseases represent the leading cause of death in developed countries despite major advances in its treatment and prevention, and these are a major cause of disability, lost productivity and increased health costs worldwide [1]
Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia
This study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy
Summary
Cardiovascular diseases represent the leading cause of death in developed countries despite major advances in its treatment and prevention, and these are a major cause of disability, lost productivity and increased health costs worldwide [1]. There is no clear evidence that MSC can differentiate into myocardial cells [8], the advantages of a MSC-based therapy could lie in the immunomodulatory effects mediated by these cells, as well as the ability of MSC to promote growth, survival or differentiation of other cells in the damaged myocardial area through paracrine mechanisms [9] These properties have encouraged pre-clinical and clinical research to explore the potential role of MSC as a cell-based treatment for heart disease [3]. Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair These cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status
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