title: Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction.
abstract: Recent studies suggest that the therapeutic effects of stem cell transplantation following myocardial infarction (MI) are mediated by paracrine factors. One of the main goals in the treatment of ischemic heart disease is to stimulate vascular repair mechanisms. Here, we sought to explore the therapeutic angiogenic potential of mesenchymal stem cell (MSC) secretions. Human MSC secretions were collected as conditioned medium (MSC-CM) using a clinically compliant protocol. Based on proteomic and pathway analysis of MSC-CM, an in vitro assay of HUVEC spheroids was performed identifying the angiogenic properties of MSC-CM. Subsequently, pigs were subjected to surgical left circumflex coronary artery ligation and randomized to intravenous MSC-CM treatment or non-CM (NCM) treatment for 7 days. Three weeks after MI, myocardial capillary density was higher in pigs treated with MSC-CM (645 ± 114 vs 981 ± 55 capillaries/mm(2); P = 0.021), which was accompanied by reduced myocardial infarct size and preserved systolic and diastolic performance. Intravenous MSC-CM treatment after myocardial infarction increases capillary density and preserves cardiac function, probably by increasing myocardial perfusion.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Timmers
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: Fatih
authors.initials: F
authors.lastname: Arslan
authors.forename: Ruenn Chai
authors.initials: RC
authors.lastname: Lai
authors.forename: Angelique A M
authors.initials: AA
authors.lastname: van Oorschot
authors.forename: Marie Jose
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Chaylendra
authors.initials: C
authors.lastname: Strijder
authors.forename: Sui Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Andree
authors.initials: A
authors.lastname: Choo
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism* / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D017077:Culture Media, Conditioned / Q000378:metabolism*; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011897:Random Allocation; D013552:Swine
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned