title: Role of tumor associated fibroblasts in human liver regeneration, cirrhosis, and cancer.
abstract: Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, and in vitro human models are missing. This paper for the first time demonstrates that (1) human neoplastic livers possess a population of multipotent adult stem cells (MASCs) with properties of TAFs; (2) a population of MASC-derived TAFs is already present in cirrhotic, not yet neoplastic, livers; (3) MASCs isolated from nonneoplastic and noncirrhotic liver scan acquire a TAF phenotype when grown in a medium conditioned by tumor cell lines, supporting the notion that TAF could originate from resident primitive cells (MASCs), possibly through a paracrine mechanism.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, P.le Kolbe 3, 33100 Udine, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cesselli
authors.forename: Antonio Paolo
authors.initials: AP
authors.lastname: Beltrami
authors.forename: Alessandra
authors.initials: A
authors.lastname: Poz
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzinotto
authors.forename: Elisa
authors.initials: E
authors.lastname: Comisso
authors.forename: Natascha
authors.initials: N
authors.lastname: Bergamin
authors.forename: Evgenia
authors.initials: E
authors.lastname: Bourkoula
authors.forename: Anja
authors.initials: A
authors.lastname: Pucer
authors.forename: Elisa
authors.initials: E
authors.lastname: Puppato
authors.forename: Barbara
authors.initials: B
authors.lastname: Toffoletto
authors.forename: Marisa
authors.initials: M
authors.lastname: Sorrentino
authors.forename: Umberto
authors.initials: U
authors.lastname: Baccarani
authors.forename: Claudio
authors.initials: C
authors.lastname: Avellini
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Beltrami