Liver Mesenchymal Thy-1 Cells: Important Player In Oval Cell Mediated Liver Regeneration

Recently, we and others have reported that Thy1 antigen is expressed in rat liver myofibroblasts. To study further the properties and the function of these cells, we purified Thy‐1 + cells by MACS and FACS and analyzed their gene expression pattern using Affymetrix Rat expression array 230 2.0, RT‐PCR and IF microscopy. Thy‐1 + cells are highly activated in models of oval cell‐mediated liver regeneration, tightly surrounding the oval cell pseudoducts. Thy‐1 + cells appear, proliferate and disappear from the liver in parallel with oval cells. Thy‐1 + cells express mRNA for genes considered specific for stellate cells: desmin, v‐cam, gfap, pdgfrβ, integrin β3; for myofibroblasts: αsma, elastin, fibulin‐2, fibrilin‐1; for matrix remodeling proteins: mmp2, collagen I‐a1, ‐a2, III and IV; for mesenchymal stromal cells: CD54, CD73, CD105, CD166, SDF‐1; and for growth factors and cytokines that can stimulate oval cell growth: Il‐6, hgf, tweak. Co‐expression of Thy‐1 antigen with desmin, αSma and Pdgfrβ was confirmed by double IF microscopy. RT‐PCR analysis of isolated individual Thy‐1 expressing clones confirmed the heterogeneity of these cells. Conclusion: liver mesenchymal Thy‐1 + cells are the major supporting cells in the oval cells niche. Supported by NIH grant R01 DK59321 (to M.D.D.)