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Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: Engraftment and hepatocyte differentiation versus profibrogenic potential
  1. Lorenzo Valfrè di Bonzo (lorenzo.valfre{at}unito.it)
  1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
    1. Ivana Ferrero (ivana.ferrero{at}unito.it)
    1. Università di Torino, Dept. Pediatrics, Italy
      1. Carlo Cravanzola (carlo.cravanzola{at}unito.it)
      1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
        1. Katia Mareschi (katia.mareschi{at}unito.it)
        1. Universita degli Studi di Torino, Dept. Pediatrics, Italy
          1. Deborah Rustichelli (deborah.rustichelli{at}unito.it)
          1. Universita degli Studi di Torino, Dept. Pediatrics, Italy
            1. Erica Novo (erica.novo{at}unito.it)
            1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
              1. Fiorella Sanavio (fiorella.sanavio{at}unito.it)
              1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                1. Stefania Cannito (stefania.cannito{at}unito.it)
                1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                  1. Elena Zamara (elena.zamara{at}unito.it)
                  1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                    1. Manuela Bertero
                    1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                      1. Annalisa Davit (annalisa.davit{at}unito.it)
                      1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                        1. Simona Francica (simona.francica{at}unito.it)
                        1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                          1. Francesco Novelli (francesco.novelli{at}unito.it)
                          1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                            1. Sebastiano Colombatto (sebastiano.colombatto{at}unito.it)
                            1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy
                              1. Franca Fagioli (franca.fagioli{at}unito.it)
                              1. Universita degli Studi di Torino, Dept. Pediatrics, Italy
                                1. Maurizio Parola (maurizio.parola{at}unito.it)
                                1. Universita degli Studi di Torino, Dept. Exp. Med. Oncol., Italy

                                  Abstract

                                  Background and aim Mesenchymal stem cells from bone marrow (MSC) may have the potential to differentiate in vitro and in vivo into hepatocytes. We investigated whether transplanted human MSC (hMSC) may engraft the liver of non-obese diabetic severe combined immuno-deficient (NOD/SCID) mice and differentiate into cells of hepatic lineage.

                                  Methods Ex-vivo expanded, highly purified and functionally active hMSC from bone marrow were transplanted (caudal vein) in sublethally irradiated NOD/SCID mice that were either exposed or not to acute liver injury or submitted to a protocol of chronic injury (single or chronic i.p. injection of CCl4, respectively). Chimeric livers were analysed for expression of human transcripts and antigens.

                                  Results Liver engraftment of cells of human origin was very low in normal and acutely injured NOD/SCID mice with significantly higher numbers found in chronically injured livers. However, hepatocellular differentiation was relatively rare limited to a low number of cells (ranging from less than 0.1 % to 0.23 %) as confirmed by very low or not detectable levels of human transcripts for alfa-FP, CK18, CK19 and albumin in either normal or injured livers. Finally, a significant number of cells of human origin exhibited a myofibroblast - like morphology.

                                  Conclusions Transplanted hMSC have the potential to migrate into normal and injured liver parenchyma, particularly under conditions of chronic injury, but differentiation into hepatocyte-like cells is a rare event and pro-fibrogenic potential of hMSC transplant should be not underevaluated.

                                  • hepatocyte differentiation
                                  • human mesenchymal stem cells
                                  • liver engraftment
                                  • liver fibrosis
                                  • transplantation of stem cells

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