Abstract 16820: Human Vascular Pericytes and Cardiac Stem Cells for Specialized Stimulation of Neovascularization and Cardiomyogenesis of the Infarcted Heart
Background: Both vascular and myocardial cells are essential for effective cardiac repair. Here, we investigate whether co-transplantation of adventitial pericytes (APs) from saphenous vein leftovers of patients undergoing coronary artery bypass graft (CABG) surgery and c-Kit+ cardiac stem cells (CSCs) from transplantation donor hearts could synergistically improve cardiac recovery in a mouse model of acute myocardial infarction (MI).
Results: Viability and purity of cell preparations were verified before transplantation. SCID-beige immuno-deficient mice were subjected to operative MI and randomly allocated to peri-infarct injection of APs, CSCs, APs+CSCs (each at 300000/heart) or vehicle (V) (n=10 per group). As previously shown, APs improved pressure indexes (dP/dtmax [mean±SE]: 4250±142 vs 3828±78 mmHg in V, p=0.02), and both volumetric (LVESV: 35±8 vs 87±1 μ l, p<0.001; LVEDV: 69±11 vs 112±2 μ l, p<0.001) and functional parameters (LVEF: 52±5 vs 22±1%, p<0.001; CO: 17±2 vs 12±1 ml/min, p=0.004) at 14-days post-MI. CSCs alone also improved volumetric indexes (LVESV: 46±10 and LVEDV: 77±8 μ l, p<0.001) and LVEF (43±6%, p<0.001) but not CO or pressure indexes (not shown). APs+CSCs failed to induce additive effects compared to APs alone (dP/dtmax: 4364±194 mmHg, LVESV: 42±6 μ l, LVEDV: 79±9 μ l; LVEF 48±3%; CO: 18 ±1 ml/min). APs are known to release factors that evoke an angiocrine response in the host and could also attract host stem cells in a paracrine manner. Consistently, AP conditioned medium (CM) stimulated CSC migration by 7-fold, when compared to non-conditioned medium (NCM). CSC chemo-attraction was even greater when using CM from hypoxia-challenged APs (14-fold vs. NCM). We identified VEGF and HGF among the most abundantly secreted factors in AP CM. In line, 14-days post-MI, there is a ∼20-fold increase in endogenous c-Kit+ CSC abundance in the peri-infarct zone of AP-injected hearts.
Conclusions: These data indicate that, in addition to their angiocrine activity, APs enhance recovery of the ischemic heart by attracting endogenous CSCs via an as yet unidentified paracrine mechanism; this AP-evoked host response appears to be robust since co-therapy of APs and CSCs does further improve AP therapy alone.
- © 2012 by American Heart Association, Inc.