Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.

Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellu...

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Autores principales:	Nicole A Hofmann, Anna Ortner, Rodrigo O Jacamo, Andreas Reinisch, Katharina Schallmoser, Rokhsareh Rohban, Nathalie Etchart, Margareta Fruehwirth, Christine Beham-Schmid, Michael Andreeff, Dirk Strunk
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8624d9cddce540539aab93e4837894c4
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spelling	oai:doaj.org-article:8624d9cddce540539aab93e4837894c42021-11-18T07:06:16ZOxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.1932-620310.1371/journal.pone.0044468https://doaj.org/article/8624d9cddce540539aab93e4837894c42012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22970226/?tool=EBIhttps://doaj.org/toc/1932-6203Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellular compartments responsible for hypoxia response during vasculogenesis. Mesenchymal stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription factor (HIF)-1α earlier and more sensitively than endothelial colony forming progenitor cells (ECFCs) in vitro and in vivo. Hypoxic ECFCs showed reduced function in vitro and underwent apoptosis within 24h in vivo when used without MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF-1α abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting in the formation of patent perfused human vessels. Several angiogenic factors need to act in concert to partially substitute mesenchymal HIF-deficiency. Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to initiate vasculogenesis in vivo and to bypass hypoxia-induced apoptosis. We describe a novel mechanistic role of MSPCs as oxygen sensors promoting vasculogenesis thus underscoring their importance for the development of advanced cellular therapies.Nicole A HofmannAnna OrtnerRodrigo O JacamoAndreas ReinischKatharina SchallmoserRokhsareh RohbanNathalie EtchartMargareta FruehwirthChristine Beham-SchmidMichael AndreeffDirk StrunkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44468 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole A Hofmann Anna Ortner Rodrigo O Jacamo Andreas Reinisch Katharina Schallmoser Rokhsareh Rohban Nathalie Etchart Margareta Fruehwirth Christine Beham-Schmid Michael Andreeff Dirk Strunk Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
description	Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellular compartments responsible for hypoxia response during vasculogenesis. Mesenchymal stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription factor (HIF)-1α earlier and more sensitively than endothelial colony forming progenitor cells (ECFCs) in vitro and in vivo. Hypoxic ECFCs showed reduced function in vitro and underwent apoptosis within 24h in vivo when used without MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF-1α abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting in the formation of patent perfused human vessels. Several angiogenic factors need to act in concert to partially substitute mesenchymal HIF-deficiency. Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to initiate vasculogenesis in vivo and to bypass hypoxia-induced apoptosis. We describe a novel mechanistic role of MSPCs as oxygen sensors promoting vasculogenesis thus underscoring their importance for the development of advanced cellular therapies.
format	article
author	Nicole A Hofmann Anna Ortner Rodrigo O Jacamo Andreas Reinisch Katharina Schallmoser Rokhsareh Rohban Nathalie Etchart Margareta Fruehwirth Christine Beham-Schmid Michael Andreeff Dirk Strunk
author_facet	Nicole A Hofmann Anna Ortner Rodrigo O Jacamo Andreas Reinisch Katharina Schallmoser Rokhsareh Rohban Nathalie Etchart Margareta Fruehwirth Christine Beham-Schmid Michael Andreeff Dirk Strunk
author_sort	Nicole A Hofmann
title	Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
title_short	Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
title_full	Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
title_fullStr	Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
title_full_unstemmed	Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
title_sort	oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8624d9cddce540539aab93e4837894c4
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Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.

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