Hepatic perivascular mesenchymal stem cells with myogenic properties.

Abstract

Pericytes are multipotent mesenchymal stem cells located on the walls of blood vessels in various organs and are characterized as CD146+ cells. In this study, we first immunohistochemically detected pericytes in the perivascular regions of liver from two mouse genotypes, namely wild-type (WT) and myostatin null (Mstn-/- ). We further isolated pericytes using sorting as CD146+ CD34- CD56- CD45- cells. The main finding of this study involves the contrasting fibrogenic vs. myogenic behaviour of liver pericytes from WT and Mstn-/- mice, respectively. Sorted CD146+ liver pericytes (WT and Mstn-/- ) expressed PDGFRβ, NG2, vimentin, adult stem cell markers CD73, CD105, CD44 and could be readily differentiated into adipogenic, osteogenic and chondrogenic lineages. Furthermore, these CD146+ cells from WT and Mstn-/- livers did not express myostatin, in contrast to the total liver tissue of WT. The absence of αSMA and GFAP made these cells easily distinguishable from hepatic stellate cells. When subjected to standard myogenic differentiation with low serum the CD146+ cells from WT liver differentiated into myofibroblasts (fibrogenic) and the CD146+ cells from Mstn-/- liver differentiated into multinucleated myotubes (myogenic). Finally, we transplanted CD146+ pericytes into tibialis anterior muscle of dystrophic mice and established the generation of novel myofibres, thereby proving their cell therapy potential. The liver tissue microenvironment with myostatin in WT and the absence of myostatin in Mstn-/- conditions might exert a paracrine effect in determining the fate of pericyte-like cells in the liver.