title: Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo.
abstract: Stem cell therapies are promising strategies to regenerate human injured tissues, including ischemic myocardium. Here, we examined the acquisition of properties associated with vascular growth by human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs), and whether they promoted vascular growth in vivo. UCBMSCs were induced in endothelial cell-specific growth medium (EGM-2) acquiring new cell markers, increased Ac-LDL uptake, and migratory capacity as assessed by qRT-PCR, Western blotting, indirect immunofluorescence, and invasion assays. Angiogenic and vasculogenic potentials could be anticipated by in vitro experiments showing self organization into Matrigel-mediated cell networks, and activation of circulating angiogenic-supportive myeloid cells. In mice, following subcutaneous co-injection with Matrigel, UCBMSCs modified to co-express bioluminescent (luciferases) and fluorescent proteins were demonstrated to participate in the formation of new microvasculature connected with the host circulatory system. Response of UCBMSCs to ischemia was explored in a mouse model of acute myocardial infarction (MI). UCBMSCs transplanted using a fibrin patch survived 4 weeks post-implantation and organized into CD31(+)network structures above the infarcted myocardium. MI-treated animals showed a reduced infarct scar and a larger vessel-occupied area in comparison with MI-control animals. Taken together, the presented results show that UCBMSCs can be induced in vitro to acquire angiogenic and vasculogenic properties and contribute to vascular growth in vivo.
authors.affiliation: ICREC Research Program, Fundació Institut dInvestigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Roura
authors.forename: Juli R
authors.initials: JR
authors.lastname: Bagó
authors.forename: Carolina
authors.initials: C
authors.lastname: Soler-Botija
authors.forename: Josep M
authors.initials: JM
authors.lastname: Pujal
authors.forename: Carolina
authors.initials: C
authors.lastname: Gálvez-Montón
authors.forename: Cristina
authors.initials: C
authors.lastname: Prat-Vidal
authors.forename: Aida
authors.initials: A
authors.lastname: Llucià-Valldeperas
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Blanco
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayes-Genis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003094:Collagen; D003470:Culture Media; D004338:Drug Combinations; D005312:Fetal Blood / Q000166:cytology*; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007797:Laminin; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000209:etiology*; D017202:Myocardial Ischemia / Q000150:complications / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003470:Culture Media; D004338:Drug Combinations; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen