Combined Intramyocardial Delivery of Human Pericytes and Cardiac Stem Cells Additively Improves the Healing of Mouse Infarcted Hearts Through Stimulation of Vascular and Muscular Repair
Rationale: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities.
Objective: Compare the reparative potential of Saphenous Vein-derived Pericytes (SVPs) with that of Cardiac Stem Cells (CSCs) in a model of myocardial infarction (MI), and investigate if combined cell transplantation provides further improvements.
Methods and Results: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery (CABG) and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300,000 cells of each type/heart) was tested in infarcted SCID-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post-MI. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of HGF, VEGF, FGF, SCF and SDF-1, while SVPs release higher quantities of Angiopoietins and miR-132. Co-culture of the two cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of SDF-1 was synergistically augmented along with down-regulation of SDF-1 degrading enzyme DPP-4.
Conclusions: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
- cell therapy
- cardiac stem cell
- mouse model
- acute myocardial infarction
- cell transplantation
- cardiac remodeling
- Received January 29, 2015.
- Revision received February 27, 2015.
- Accepted March 23, 2015.