title: Pigment epithelium-derived factor (PEDF) peptide promotes the expansion of hepatic stem/progenitor cells via ERK and STAT3-dependent signaling.
abstract: Hepatic stem/progenitor cells (HPC) have been considered as a potential cell source of an alternative to liver transplantation. Production of large numbers of autologous HPC from small pieces of live tissue is crucial for the application of HPC-based liver therapy. In this study, we demonstrated that a synthetic 44-amino acid peptide (44-mer) derived from pigment epithelium-derived factor (PEDF) can facilitate the production of a large number of actively dividing HPC from normal adult rat livers in a 35-day culture period. The phenotypic properties of HPC were characterized by morphological observation, colony formation and high expression of classical HPC markers including epithelial cell adhesion molecule (EpCAM), leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and tumor-associated calcium signal transducer (TROP2). The 44-mer stimulated HPC proliferation in vitro and in mouse livers injured by a single intraperitoneal injection of carbon tetrachloride. In addition, the 44-mer induced the phosphorylation of ERK1/2 and STAT3 in HPC. Blocking the activity of ERK or STAT3 with pharmacological inhibitors attenuated the effects of the 44-mer on the induction of HPC proliferation. The long-term expanded HPC still possessed a bipotent ability to differentiate towards bile duct cells and mature hepatocytes. These results imply that the PEDF peptide may be a simple and effective agent to improve HPC-based liver therapy.
authors.affiliation: Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College No. 92 Zhongshan North Road, Taipei, Taiwan.
authors.forename: Shou-Chuan
authors.initials: SC
authors.lastname: Shih
authors.affiliation: Department of Medical Research, Ophthalmology, Mackay Memorial Hospital No. 92 Zhongshan North Road, Taipei, Taiwan.
authors.forename: Tsung-Chuan
authors.initials: TC
authors.lastname: Ho
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University No. 1 Jen Ai Road, Section 1, Taipei, Taiwan.
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Ophthalmology, Mackay Memorial Hospital No. 92 Zhongshan North Road, Taipei, Taiwan.
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
keywords: PEDF; growth factor; liver; peptide; stem cell