title: Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells in cardiac repair.
abstract: Whereas cardiac-derived c-kit(+) stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (MSCs) are undergoing clinical trials testing safety and efficacy as a cell-based therapy, the relative therapeutic and biologic efficacy of these two cell types is unknown. We hypothesized that human CSCs have greater ability than MSCs to engraft, differentiate, and improve cardiac function. We compared intramyocardial injection of human fetal CSCs (36,000) with two doses of adult MSCs (36,000 and 1,000,000) or control (phosphate buffered saline) in nonobese diabetic/severe combined immune deficiency mice after coronary artery ligation. The myocardial infarction-induced enlargement in left ventricular chamber dimensions was ameliorated by CSCs (p < .05 for diastolic and systolic volumes), as was the decline in ejection fraction (EF; p < .05). Whereas 1 × 10(6) MSCs partially ameliorated ventricular remodeling and improved EF to a similar degree as CSCs, 36,000 MSCs did not influence chamber architecture or function. All cell therapies improved myocardial contractility, but CSCs preferentially reduced scar size and reduced vascular afterload. Engraftment and trilineage differentiation was substantially greater with CSCs than with MSCs. Adult-cultured c-kit(+)CSCs were less effective than fetal, but were still more potent than high-dose MSCs. These data demonstrate enhanced CSC engraftment, differentiation, and improved cardiac remodeling and function in ischemic heart failure. MSCs required a 30-fold greater dose than CSCs to improve cardiac function and anatomy. Together, these findings demonstrate a greater potency of CSCs than bone marrow MSCs in cardiac repair.
authors.affiliation: Interdisciplinary Stem Cell Institute, Mille School of Medicine, University of MIami, Florida 33136, USA.
authors.forename: Behzad N
authors.initials: BN
authors.lastname: Oskouei
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamirault
authors.forename: Chacko
authors.initials: C
authors.lastname: Joseph
authors.forename: Adriana V
authors.initials: AV
authors.lastname: Treuer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Landa
authors.forename: Jose
authors.initials: J
authors.lastname: Da Silva
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Hatzistergos
authors.forename: Marc
authors.initials: M
authors.lastname: Dauer
authors.forename: Wayne
authors.initials: W
authors.lastname: Balkan
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D053686:Fetal Stem Cells / Q000378:metabolism* / Q000502:physiology; D006334:Heart Function Tests; D006439:Hemodynamics; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D033581:Stem Cell Transplantation; D020257:Ventricular Remodeling
chemical_list: D019009:Proto-Oncogene Proteins c-kit