Michael Oertel, PhD
Michael Oertel, PhD
Department of Pathology
S404 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
Research Interests: Stem/progenitor cells, Mechanisms of tissue replacement, Cell-based therapy strategies in fibrotic microenvironments
Our research projects are focused on the development of novel cell-based strategies to replace injured hepatic tissue mass and restore liver function. We have established cell transplantation models in rats that represent excellent tools to study the mechanism(s) of tissue replacement by stem/progenitor cells or mature hepatocytes under non-selective conditions and in liver environments that resemble human disorders.
To date, fetal liver stem/progenitor cells derived from wt. DPPIV+ F344 rats represent the most efficient cell population, which is capable of repopulating the (near)-normal liver of DPPIV– F344 rats. Previously, we demonstrated that transplanted stem/progenitor cells have a growth advantage through their resistance to activin A, an inducer of cell cycle arrest and apoptosis, and are capable of repopulating the recipient liver through a mechanism akin to cell competition. Our studies are aimed to investigate the mechanism of activin A-mediated growth attenuation in hepatic cells in vitro and elucidate the possible role of activin A in creating a permissive or stimulatory microenvironment in recipient livers for transplanted cells. In these studies, we are currently generating AAV-based vector systems for in vivo gene delivery in recipient livers in order to modulate local microenvironments and augment repopulation by transplanted hepatic cells. Furthermore, we have developed a detection method for transplanted cells, which allows us to isolate RNA of high quality from laser capture-microdissected (LCM) donor-derived cell clusters and surrounding host hepatic parenchyma. By analyzing amplified LCM-derived RNA using qRT-PCR and microarray analyses, these studies are focused on identifying genes that are crucial for hepatic tissue replacement.
Recently, we demonstrated Proof of concept that donor-derived cells can replace injured hepatic tissue mass in a microenvironment with advanced fibrosis (induced by TAA) and anti-fibrotic effects can be achieved utilizing experimental conditions that reflect circumstances similar to human fibrosis/cirrhosis. In addition, biliary fibrosis (following bile duct ligation) stimulates phenotype transition of hepatocytes towards a biliary epithelial cell type. The mechanism of tissue replacement by transplanted cells, as well as phenotype conversion is being investigated in these fibrosis models. Furthermore, our studies are aimed to explore whether restoration of impaired hepatocyte function following tissue replacement in fibrotic liver regulates paracrine mediators that are involved in progression of fibrosis.
Special Interest Groups:
Chronic Liver Injury