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Endothelial cell fitness dictates the source of regenerating liver vasculature

Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transpla...

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Autores principales: Singhal, Mahak, Liu, Xiaoting, Inverso, Donato, Jiang, Kai, Dai, Jianing, He, Hao, Bartels, Susanne, Li, Weiping, Abdul Pari, Ashik Ahmed, Gengenbacher, Nicolas, Besemfelder, Eva, Hui, Lijian, Augustin, Hellmut G., Hu, Junhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170182/
https://www.ncbi.nlm.nih.gov/pubmed/30194265
http://dx.doi.org/10.1084/jem.20180008
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author Singhal, Mahak
Liu, Xiaoting
Inverso, Donato
Jiang, Kai
Dai, Jianing
He, Hao
Bartels, Susanne
Li, Weiping
Abdul Pari, Ashik Ahmed
Gengenbacher, Nicolas
Besemfelder, Eva
Hui, Lijian
Augustin, Hellmut G.
Hu, Junhao
author_facet Singhal, Mahak
Liu, Xiaoting
Inverso, Donato
Jiang, Kai
Dai, Jianing
He, Hao
Bartels, Susanne
Li, Weiping
Abdul Pari, Ashik Ahmed
Gengenbacher, Nicolas
Besemfelder, Eva
Hui, Lijian
Augustin, Hellmut G.
Hu, Junhao
author_sort Singhal, Mahak
collection PubMed
description Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis in livers with intact endothelium was solely mediated by proliferation of resident ECs. However, following irradiation-induced EC damage, bone marrow–derived mononuclear cells were recruited and incorporated into the vasculature. Further experiments with direct bone marrow infusion or granulocyte colony–stimulating factor (G-CSF)–mediated progenitor cell mobilization, which resembles clinically relevant stem cell therapy, demonstrated that bone marrow–derived cells did not contribute to the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx). Taken together, the data reconcile many of the discrepancies in the literature and highlight that the cellular source of regenerating endothelium depends on the fitness of the residual vasculature.
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spelling pubmed-61701822019-04-01 Endothelial cell fitness dictates the source of regenerating liver vasculature Singhal, Mahak Liu, Xiaoting Inverso, Donato Jiang, Kai Dai, Jianing He, Hao Bartels, Susanne Li, Weiping Abdul Pari, Ashik Ahmed Gengenbacher, Nicolas Besemfelder, Eva Hui, Lijian Augustin, Hellmut G. Hu, Junhao J Exp Med Research Articles Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis in livers with intact endothelium was solely mediated by proliferation of resident ECs. However, following irradiation-induced EC damage, bone marrow–derived mononuclear cells were recruited and incorporated into the vasculature. Further experiments with direct bone marrow infusion or granulocyte colony–stimulating factor (G-CSF)–mediated progenitor cell mobilization, which resembles clinically relevant stem cell therapy, demonstrated that bone marrow–derived cells did not contribute to the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx). Taken together, the data reconcile many of the discrepancies in the literature and highlight that the cellular source of regenerating endothelium depends on the fitness of the residual vasculature. Rockefeller University Press 2018-10-01 /pmc/articles/PMC6170182/ /pubmed/30194265 http://dx.doi.org/10.1084/jem.20180008 Text en © 2018 Singhal et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Singhal, Mahak
Liu, Xiaoting
Inverso, Donato
Jiang, Kai
Dai, Jianing
He, Hao
Bartels, Susanne
Li, Weiping
Abdul Pari, Ashik Ahmed
Gengenbacher, Nicolas
Besemfelder, Eva
Hui, Lijian
Augustin, Hellmut G.
Hu, Junhao
Endothelial cell fitness dictates the source of regenerating liver vasculature
title Endothelial cell fitness dictates the source of regenerating liver vasculature
title_full Endothelial cell fitness dictates the source of regenerating liver vasculature
title_fullStr Endothelial cell fitness dictates the source of regenerating liver vasculature
title_full_unstemmed Endothelial cell fitness dictates the source of regenerating liver vasculature
title_short Endothelial cell fitness dictates the source of regenerating liver vasculature
title_sort endothelial cell fitness dictates the source of regenerating liver vasculature
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170182/
https://www.ncbi.nlm.nih.gov/pubmed/30194265
http://dx.doi.org/10.1084/jem.20180008
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