title: Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats.
abstract: The ability of the liver to regenerate is crucial to protect liver function after injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in liver sinusoidal endothelial cells (LSECs) are thought to drive liver regeneration. However, in contrast to endothelial progenitor cells, mature LSECs express little HGF. Therefore, we sought to establish in rats whether liver injury causes BM LSEC progenitor cells to engraft in the liver and provide increased levels of HGF and to examine the relative contribution of resident and BM LSEC progenitors. LSEC label-retaining cells and progenitors were identified in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the circulation doubled. In the liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs. When irradiated rats underwent partial hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors rescued the defect. Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and were more proliferative than resident LSEC progenitors after partial hepatectomy. Resident LSEC progenitors within their niche may play a smaller role in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these progenitors engrafted and expanded markedly over a 2-month period. In conclusion, LSEC progenitor cells are present in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regeneration.
authors.affiliation: Division of Gastrointestinal and Liver Disease and University of Southern California Research Center for Liver Disease, Los Angeles, California 90033, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Xie
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Colin K
authors.initials: CK
authors.lastname: Hill
authors.forename: Laurie D
authors.initials: LD
authors.lastname: DeLeve
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002455:Cell Division; D019070:Cell Lineage; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology*; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000502:physiology / Q000648:ultrastructure; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011828:Radiation Chimera; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
chemical_list: D017228:Hepatocyte Growth Factor