Immunomodulation of cell transplants derived after reprogramming of MSC in a model of Crigler Najjar syndrome

• Applicant: Dr. Vanessa Sandfort
• Subject Area: Gastroenterology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218739263

Orthotopic liver transplantation is often the only option to cure inherited metabolic liver diseases. Transplantation of hepatocytes can serve as an alternative therapy, but the availability of hepatocytes is low due to the shortage of liver donors. In order to find alternative cells which can be used for therapy of liver diseases, other sources of hepatocytes have to be found, e.g. generation of hepatocytes from mesenchymal stem cells (MSC) or from induced pluripotent stem cells (iPS). MSCs have several advantages such as low immunogenicity and immunomodulatory capabilities while iPS cells have the advantage of pluripotency. In the current project it will be investigated whether the immunomodulatory effects of MSCs are maintained after reprogramming and also after hepatocyte differentiation. Cell transplants will be analyzed in vitro by molecular and immunologic methodology and in the Gunn rat model of Crigler-Najjar syndrome-1, an inherited metabolic liver disease. Cells will be derived from congeneic and also from allogeneic donors in order to explore the extent of immunomodulatation. Also, the question will be addressed whether administration of immunosuppressants can be decreased or omitted. iPS cells derived from fibroblasts will serve as a control.The results of the project will improve the understanding of stem cell biology in a clinical related transplantation model. The approach used here may also be relevant for cell-based therapy of other organs where organ shortage and immunosuppression are of consideration.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Jayanta Roy-Chowdhury