Khalil, M.,
"Direct contact of umbilical cord blood endothelial progenitors with living cardiac tissue is a requirement for vascular tube-like structures formation",
J. Cell. Mol. Med, vol. 15, issue 9, pp. 1914-1926, 2010.
AbstractThe umbilical cord blood derived endothelial progenitor cells (EPCs) contribute to vascular regeneration in experimental models of
ischaemia. However, their ability to participate in cardiovascular tissue restoration has not been elucidated yet. We employed a novel
coculture system to investigate whether human EPCs have the capacity to integrate into living and ischaemic cardiac tissue, and participate
to neovascularization. EPCs were cocultured with either living or ischaemic murine embryonic ventricular slices, in the presence
or absence of a pro-angiogenic growth factor cocktail consisting of VEGF, IGF-1, EGF and bFGF. Tracking of EPCs within the cocultures
was performed by cell transfection with green fluorescent protein or by immunostaining performed with anti-human vWF, CD31, nuclei
and mitochondria antibodies. EPCs generated vascular tube-like structures in direct contact with the living ventricular slices.
Furthermore, the pro-angiogenic growth factor cocktail reduced significantly tubes formation. Coculture of EPCs with the living
ventricular slices in a transwell system did not lead to vascular tube-like structures formation, demonstrating that the direct contact is
necessary and that the soluble factors secreted by the living slices were not sufficient for their induction. No vascular tubes were formed
when EPCs were cocultured with ischaemic ventricular slices, even in the presence of the pro-angiogenic cocktail. In conclusion, EPCs
form vascular tube-like structures in contact with living cardiac tissue and the direct cell-to-cell interaction is a prerequisite for their
induction. Understanding the cardiac niche and micro-environmental interactions that regulate EPCs integration and neovascularization
are essential for applying these cells to cardiovascular regeneration.
Khalil, M.,
"Direct contact of umbilical cord blood endothelial progenitors with living cardiac tissue is a requirement for vascular tube-like structures formation",
J. Cell. Mol. Med, vol. 15, issue 9, pp. 1914-1926, 2010.
AbstractThe umbilical cord blood derived endothelial progenitor cells (EPCs) contribute to vascular regeneration in experimental models of
ischaemia. However, their ability to participate in cardiovascular tissue restoration has not been elucidated yet. We employed a novel
coculture system to investigate whether human EPCs have the capacity to integrate into living and ischaemic cardiac tissue, and participate
to neovascularization. EPCs were cocultured with either living or ischaemic murine embryonic ventricular slices, in the presence
or absence of a pro-angiogenic growth factor cocktail consisting of VEGF, IGF-1, EGF and bFGF. Tracking of EPCs within the cocultures
was performed by cell transfection with green fluorescent protein or by immunostaining performed with anti-human vWF, CD31, nuclei
and mitochondria antibodies. EPCs generated vascular tube-like structures in direct contact with the living ventricular slices.
Furthermore, the pro-angiogenic growth factor cocktail reduced significantly tubes formation. Coculture of EPCs with the living
ventricular slices in a transwell system did not lead to vascular tube-like structures formation, demonstrating that the direct contact is
necessary and that the soluble factors secreted by the living slices were not sufficient for their induction. No vascular tubes were formed
when EPCs were cocultured with ischaemic ventricular slices, even in the presence of the pro-angiogenic cocktail. In conclusion, EPCs
form vascular tube-like structures in contact with living cardiac tissue and the direct cell-to-cell interaction is a prerequisite for their
induction. Understanding the cardiac niche and micro-environmental interactions that regulate EPCs integration and neovascularization
are essential for applying these cells to cardiovascular regeneration.