Therapeutic potential of adult stem cell-derived hepatocytes in alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive genetic disorder associated with pulmonary diseases and liver cirrhosis. The mutation in the SERPINA gene locus leads to misfolding of the protein alpha-1 antitrypsin (AAT), which accumulates in the endoplasmic reticulum of hepatocytes causing cell death. This injury is strongly associated with liver fibrosis, cirrhosis and finally end-stage liver failure. During this process the liver parenchyma is replaced by connective tissue, particularly collagen type I secreted by transformed hepatic stellate cells. Currently, liver transplantation is the only therapeutic option with the potential to correct the principle cause of the disease. The transplanted organ then corrects the metabolic defect at least in part by production and secretion of AAT into the patient's blood stream thus protecting tissues from proteolytic damage. The current shortage of donor livers, however, even limits the clinical implementation of this option. Therefore, novel therapeutic approaches are needed. Assuming that the hepatocyte is the smallest functional entity of the liver, transplantation of hepatocytes or of hepatocyte-like cells generated from adult stem cells represents such a new therapeutic strategy. Protocols were developed to differentiate adult mesenchymal stem cells into functional hepatocyte-like cells in vitro and in vivo. The aim of this project is to provide preclinical data on the therapeutic potential of stem cell-derived hepatocytes to correct for (AATD) in the liver. In a transgenic mouse model the improvement of AATD by transplanted stem cell-derived hepatocytes will be investigated. Biochemical and histological analysis will give information on liver tissue integrity and function as well as the underlying mechanisms on the molecular level. Data generated in this study are the basis for the design of a phase I clinical trial to assess safety in the clinical setting of AATD.

Curriculum Vitae of Sandra Pelz

Sandra Pelz has completed her undergraduate degree in Nutritional Sciences at the Martin-Luther-University of Halle-Wittenberg, Germany. Since May 2010 she has been a postgraduate research fellow at the Center of Applied Medical and Human Biological Research of the University Clinic of Halle-Wittenberg and is studying towards a PhD. Ms Pelz' main interests of research have been non-alcoholic Steatohepatitis and cell transplantation.

Her current research project "Therapeutic potential of adult stem cell-derived hepatocytes in alpha-1 antitrypsin deficiency" focuses on the therapeutic potential of adult stem cell-derived hepatocytes in alpha-1 antitrypsin deficiency.

Contact
Sandra Pelz
Martin-Luther-University Halle-Wittenberg
1st Dept. of Internal Medicine
Center of Applied Medical and Human Biological Research
Molecular Hepatology
Heinrich-Damerow-Straße 1
06097 Halle/Saale, Germany