Journal Article

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Promote Vascular Growth In Vivo

Roura, Santiago, Llucià-Valldeperas, Aida, Blanco, Jerónimo, Bagó, Juli R., Soler-Botija, Carolina, Bayes-Genis, Antoni, Pujal, Josep M., Gálvez-Montón, Carolina, Prat-Vidal, Cristina

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis of Variance / Angiogenesis / Animal tissues / Animals / Bioengineering / Biology / Biomedical materials / Biomedical research / Blood / Blotting, Western / Bone marrow / Cell activation / Cell adhesion & migration / Cell growth / Circulatory system / Coinjection / Collagen / Cord blood / Culture Media / Drug Combinations / Endothelial cells / Fetal Blood - cytology / Fibrin / Fibroblasts / Fluorescein Angiography / Fluorescence / Fluorescent Antibody Technique, Indirect / Gene expression / Growth / Heart attacks / Heart failure / Humans / Immunofluorescence / Implantation / Ischemia / Kinases / Laminin / Low density lipoprotein / Low density lipoproteins / Medicine / Mesenchymal Stem Cell Transplantation - methods / Mesenchymal stem cells / Mesenchymal Stromal Cells - physiology / Mesenchyme / Mice / Mice, SCID / Microvasculature / Myeloid cells / Myocardial infarction / Myocardial Infarction - etiology / Myocardial Ischemia - complications / Myocardial Ischemia - therapy / Myocardium / Neovascularization, Physiologic - physiology / Platelet Endothelial Cell Adhesion Molecule-1 - metabolism / Proteins / Proteoglycans / Real-Time Polymerase Chain Reaction / Stem cell transplantation / Stem cells / Surgical implants / Umbilical cord / Vascular endothelial growth factor / Western blotting