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Direct Contact of Umbilical Cord Blood Endothelial Progenitors with Living Cardiac Tissue is a Requirement for Vascular Tube-like Structures Formation

Domenii publicaţii > Biologie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Lupu M., Khalil M., Iordache F., Andrei E., Pfannkuche K., Spitkovsky D., Baumgartner S., Rubach M., AbdelRazek H., Buzila C., Brockmeier K., Simionescu M., Hescheler J., Maniu H

Editorial: Journal of Cellular and Molecular Medicine, 15(9), p.1914-26, 2011.


OBJECTIVE: The umbilical cord blood derived endothelial progenitor cells (EPCs) contribute to vascular regeneration in experimental models of ischemia. However, their ability participate to 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 ischemic cardiac tissue, and participate to neovascularization. MATERIALS AND METHODS: EPCs were cocultured with either living or ischemic murine embryonic ventricular slices, in the presence or absence of a pro-angiogenic growth factor cocktail consisting of VEGF, IGF1, EGF, and bFGF. Tracking of EPCs within the cocultures was done by cell transfection with green fluorescence protein or by immunostaining using anti-human vWF, CD31, nuclei, and mitochondria antibodies. RESULTS: 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 ischemic ventricular slices, even in the presence of the pro-angiogenic cocktail. 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 microenvironmental interactions that regulate EPCs integration and neovascularization are essential for applying these cells to cardiovascular regeneration.

Cuvinte cheie: Celule progenitoare endoteliale;sange de cordon ombilical;sectiuni ventriculare;structuri vasculare tube-like;ischemie cardiaca;integrare celulara // Endothelial progenitors;umbilical cord blood;ventricular slices;vascular tube-like structures;cardiac ischemia;cellular integration