TY - JOUR
T1 - 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
AU - Avolio, Elisa
AU - Meloni, Marco
AU - Spencer, Helen
AU - Riu, Federica
AU - Katare, Rajesh
AU - Mangialardi, Giuseppe
AU - Oikawa, Atsuhiko
AU - Rodriguez-Arabaolaza, Iker
AU - Dang, Zexu
AU - Mitchell, Kathryn
AU - Reni, Carlotta
AU - Alvino, Valeria V.
AU - Rowlinson, Jonathan
AU - Livi, Ugolini
AU - Cesselli, Daniela
AU - Angelini, Gianni
AU - Emanueli, Costanza
AU - Beltrami, Antonio P.
AU - Madeddu, Paolo
PY - 2015/5/8
Y1 - 2015/5/8
N2 - 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, and investigate whether combined cell transplantation provides further improvements.Methods and Results: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. 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 hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4.Conclusions: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
AB - 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, and investigate whether combined cell transplantation provides further improvements.Methods and Results: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. 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 hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4.Conclusions: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
KW - Acute inferior myocardial infarction
KW - Cardiac remodeling, ventricular
KW - Cell transplantation
KW - Cell- and tissue-based therapy
KW - Pericytes
KW - Stem cells
U2 - 10.1161/CIRCRESAHA.115.306146
DO - 10.1161/CIRCRESAHA.115.306146
M3 - Article
C2 - 25801898
AN - SCOPUS:84928601892
SN - 0009-7330
VL - 116
SP - e81-e94
JO - Circulation Research
JF - Circulation Research
IS - 10
ER -