PLoS ONE (Jan 2012)

Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo.

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

DOI
https://doi.org/10.1371/journal.pone.0049447
Journal volume & issue
Vol. 7, no. 11
p. e49447

Abstract

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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.