title: Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis.
abstract: NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2(+) cells) that were isolated from healthy adult mouse liver by using a "Percoll-Plate-Wait" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 10(6) cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2(+) cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2(+) cells may be novel adult liver progenitors that participate in liver regeneration.
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Division of Hepatobiliary and Abdominal Organ Transplantation, Case Western Reserve University Hospital, Cleveland OH 44106, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Siegel
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shuai
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Jiejuan
authors.initials: J
authors.lastname: Lai
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Lai
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.affiliation: Hepatobiliary Institute, Southwestern Hospital, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Bai
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000502:physiology; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000378:metabolism; D033581:Stem Cell Transplantation; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4