title: Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis.
abstract: Mesenchymal stem cells or multipotent stromal cells (MSCs) have initially captured attention in the scientific world because of their differentiation potential into osteoblasts, chondroblasts and adipocytes and possible transdifferentiation into neurons, glial cells and endothelial cells. This broad plasticity was originally hypothesized as the key mechanism of their demonstrated efficacy in numerous animal models of disease as well as in clinical settings. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly caused by the multitude of bioactive molecules secreted by these remarkable cells. Numerous angiogenic factors, growth factors and cytokines have been discovered in the MSC secretome, all have been demonstrated to alter endothelial cell behavior in vitro and induce angiogenesis in vivo. As a consequence, MSCs have been widely explored as a promising treatment strategy in disorders caused by insufficient angiogenesis such as chronic wounds, stroke and myocardial infarction. In this review, we will summarize into detail the angiogenic factors found in the MSC secretome and their therapeutic mode of action in pathologies caused by limited blood vessel formation. Also the application of MSC as a vehicle to deliver drugs and/or genes in (anti-)angiogenesis will be discussed. Furthermore, the literature describing MSC transdifferentiation into endothelial cells will be evaluated critically.
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium. Electronic address: annelies.bronckaers@uhasselt.be.
authors.forename: Annelies
authors.initials: A
authors.lastname: Bronckaers
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Hilkens
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Martens
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gervois
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ratajczak
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Struys
authors.affiliation: Group of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Lambrichts
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D054338:Cell Transdifferentiation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins
keywords: Angiogenesis; Endothelial differentiation; Gene therapy; Mesenchymal stem/stromal cells; Secretome