The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver

Abstract

Their versatile biological features render mesenchymal stem cells an alternate cell resource for the treatment of liver diseases. It is important to know the mechanisms of integration of transplanted cells into the recipient tissue and to understand the communication between donor cells and the host tissue on the molecular level in order to support efficacy of cell transplantation and thus optimize the therapeutical outcome.

Anatomy, pathophysiology and basic mechanisms of disease

“…Attention also is being given to whether therapeutic delivery of engineered stem cells may be of value in treatment of liver diseases. 445,528,529 produced primarily by hepatic stellate cells, and contributes to liver fibrosis (discussed below). Stimulation of the TGFβ signalling pathway can induce G1/S phase arrest and induction of apoptosis.…”

Evidence for Bone Marrow Adult Stem Cell Plasticity: Properties, Molecular Mechanisms, Negative Aspects, and Clinical Applications of Hematopoietic and Mesenchymal Stem Cells Transdifferentiation

“…Transdifferentiation of cultured naïve MSCs into hepatocyte-like cells has been claimed to occur by adding specific differentiation media [52]. Recently Zhang et al have resumed the factors and the methods used to differentiate MSCs, from BM and other tissues, into hepatocyte-like cells underlying their liver regenerative potential [53].…”

Hepatic progenitor cells in liver regeneration: current advances and clinical perspectives

“…The question of HPCs being a continuous population with BMSCs was first raised by the following, but not all generally accepted (54,58) observations: (i) oval cells express hematopoietic markers like CD34, CD45, Thy-1and c-kit (59), (ii) invading bone marrow cells and oval cells both express CXCR4 receptor and respond to SDF-1 in massive liver injury models of oval cell-mediated liver regeneration (43), (iii) presence of Y chromosomes in the hepatocytes of female recipients of male bone marrow transplants (60). Several groups have investigated the ability of transplanted BMSCs to repop-ulate the liver (indirectly by giving rise to oval cells, or directly by transdifferentiation to hepatocytes) in different animal models of liver injury (60)(61)(62)(63)(64)(65)(66)(67)(68) of which the most notable were study of Petersen (61) in rats treated with 2-acetylaminofluorene and of Laggase (62) in an animal model of tyrosinemia type I [fumarylacetoacetate hydrolase-deficient mouse (FAH-/-mouse)]. In the latter study, HSCs transplantation completely repopulated the liver and rescued the mouse.…”