For congenital metabolic liver disorders, including hereditary tyrosinemia type 1 (HT1), orthotopic liver transplantation (OLT) is often the only possible long-term cure. Yet, the scarcity of donor organs and the complexity of the intervention significantly limits its general application. Therefore, new treatment options need to be urgently developed. Hepatocyte transplantations offer an alternative, but their limited availability, inability to significantly expand in culture, short life span and difficulties with cryopreservation necessitate the search for other sources of hepatic cells. Human skin-derived precursor cells (hSKPs) possess unique regenerative properties and can be differentiated towards hepatic precursor cells, making them well suited for cellular therapy. It has, however, been shown that the engraftment of stem cells is significantly lower compared to primary hepatocytes. In the actual postdoctoral research project, transient expression of key proteins involved in hepatocyte cell adhesion will be explored to improve in vivo liver engraftment and reduce clearance of hSKPs and their hepatic derivatives in the preclinical HT1 mouse model. This will be accomplished by mRNA electroporation of e.g. integrins, cadherins, catenins and/or matrix metalloproteinases prior to transplantation. This approach is expected to result in increased engraftment leading to significantly faster and improved therapeutic efficacy at equivalent transplanted cell numbers.
Effective start/end date1/01/1631/12/16

    Flemish discipline codes

  • Pharmacology not elsewhere classified
  • Medicinal products

    Research areas

  • Liver disorder

ID: 23797186