Partner 1: Karolinska Institutet (KI), Stockholm, Sweden 

KI is one of the world´s leading medical universities and its mission is to contribute to the improvement of human health through research and education. KI offers the Swedens broadest range of education in medicine and health sciences.

Partner 1b team leader:

Professor Stephen Strom
Department of Laboratory Medicine (LABMED)
Division of Pathology
stephen.strom@ki.se

Dr. Strom is currently a Professor of Cell Transplantation and Dr. Ewa Ellis is an Assistant Professor at Karolinska Institutet. The Strom lab has pioneered the clinical application of hepatocyte transplantation, and together the Ellis-Strom labs have created a clinical hepatocyte transplant program at KI. The Strom-Ellis labs likely have the largest experience with human hepatocyte isolation and culture in the world with over 2,300 human livers procured for cell isolation. Dr. Strom also co-developed the “humanised mouse” with Dr. Markus Grompe, the mouse model central to this application. He has recently created over 40 new iPSC lines from adult and foetal human liver, and is differentiating them to hepatocytes.

Dr. Strom will have critical functions in WP2, 3, 4 and 6 and will be principally responsible for transplantation of hepatocytes and iPS-derived hepatocytes into the FRG mice and the generation of mouse models for this project. Dr. Strom will be involved in the phenotypic analysis of mouse models and the creation and differentiation of iPSC in WP2 and will be involved in the genotypic alterations/corrections proposed in WP6. Dr. Strom will be the liaison between KI and Yecuris, for the expansion of the colonies of mice initially created at KI.  Dr. Ellis will be involved in WP2, 3 and 4 for hepatocyte isolation, mouse transplants and characterisation of stem cell-derived hepatocytes.

Dr. Strom and Ellis have extensive experience with human hepatocyte isolation, transplantation and culture and the analysis of mature human liver functions. Dr. Strom has been awarded over 15 million (USD) in research support including the Soderberg Professorship in Regenerative Medicine (2013-2017) when he relocated to Sweden from Pittsburgh. He has helped launch 2 biotech companies based on his basic research. Dr. Ellis has received >10 million SEK in research funding. Both Strom and Ellis have experience with making/analysing humanised mice and stem cell-derived hepatocytes for mature functions.

Relevant publications:

1. Hansel MC, et al. (2014) Increased reprogramming of human fetal hepatocytes compared to adult hepatocytes under feeder-free conditions. Cell Transplantation 23(1):27-38.

2. Skvorak K, et al. (2013) Placental stem cell correction of murine intermediate maple syrup urine disease. Hepatology Mar;57(3):1017-23.

3. Kim DH, et al. (2011) Fox06 integrates insulin signaling with gluconeogenesis in the liver. Diabetes 60: 2763-2774.

4. Strom SC, et al. (2010) Chimeric mice with humanised liver: tools for the study of drug metabolism, excretion, and toxicity. Methods Mol Biol. 640: 491-509.

5. Basma, H, et al. (2009) Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136:990-999.

6. Azuma H, et al. (2007) A robust system for the in vivo expansion of human hepatocytes. Nature Biotech. (2007) 25: 903-910.