TY - JOUR
AU - Singhal, Mahak
AU - Liu, Xiaoting
AU - Inverso, Donato
AU - Jiang, Kai
AU - Dai, Jianing
AU - He, Hao
AU - Bartels, Susanne
AU - Li, Weiping
AU - Abdul Pari, Ashik Ahmed
AU - Gengenbacher, Nicolas
AU - Besemfelder, Eva
AU - Hui, Lijian
AU - Augustin, Hellmut
AU - Hu, Junhao
TI - Endothelial cell fitness dictates the source of regenerating liver vasculature.
JO - Journal of experimental medicine
VL - 215
IS - 10
SN - 1540-9538
CY - New York, NY
PB - Rockefeller Univ. Press
M1 - DKFZ-2018-01447
SP - 2497-2508
PY - 2018
N1 - DKFZ-ZMBH Allianz
AB - 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.
LB - PUB:(DE-HGF)16
C6 - pmid:30194265
DO - DOI:10.1084/jem.20180008
UR - https://inrepo02.dkfz.de/record/137567
ER -