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.

Activity of mesenchymal stem cells in therapies for chronic skin wound healing

“…82 Though it has been shown that exogenous VEGF application to wounds can stimulate angiogenesis, 83 MSCs used in cell therapeutics also have been shown to stimulate EC recruitment and wound healing via VEGF secretion 33,75 or via pre-differentiation into angiogenic precursors. 84 Ultimately, MSCs are able to stimulate de novo angiogenesis in wound beds upon transplantation, a crucial factor in stimulating healing in chronic wounds that lack this normally due to the hyperinflammatory environment.…”

Erythropoietin Pretreatment of Transplanted Endothelial Colony-Forming Cells Enhances Recovery in a Cerebral Ischemia Model by Increasing Their Homing Ability: A SPECT/CT Study

“…According to the BBB disruption, we could not exclude the involvement of peripheral cell immunity even if we previously excluded the lymphocytic inflammatory reaction (4) that could be explained by the low immunogenicity of cord blood cells (16,17). Additionally, we previously reported that ECFCs did not proliferate and that only a few cells were visible 14 d after transplantation (4).…”

Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

“…MI was achieved as described previously [19]. In brief, the mice were anesthetized with a mixture of O 2 /isoflurane (2%) (Baxter International Inc., Deerfield, IL, http://www.baxter.com), intubated, and mechanically ventilated (90 breaths per minute, 0.1 ml tidal volume) using a SAR830/AP small animal ventilator (CWE, Inc., Ardmore, PA, http://www/cwe-inc.com).…”