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In Vitro Cultured Islet-Derived Progenitor Cells of Human Origin Express Human Albumin in Severe Combined Immunodeficiency Mouse Liver In Vivo

^a II. Medical Department, University of Mainz, Mainz, Germany;
^b Center for Toxicology, Institute of Legal Medicine and Rudolf-Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany;
^c Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel, Switzerland;
^d Molecular Genetics Laboratory, University Children’s Hospital, University of Mainz, Mainz, Germany;
^e Paul-Flechsig Institute, University of Leipzig, Leipzig, Germany

Key Words. Pancreas • Islet of Langerhans • Liver • Stem cell

Correspondence: Marc-Alexander von Mach, M.D., II. Medical Department, Langenbeckstr. 1, 55131 Mainz, Germany. Telephone: 49-6131-174154; Fax: 49-6131-176605; e-mail: marcm{at}giftinfo.uni-mainz.de

Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult pancreas that may give rise to liver cells in vivo. The aim of the present study was to determine the ability of human islet-derived cells to adopt a hepatic phenotype in vivo. Cultured human islet-derived progenitor cells that did not express albumin in vitro were stained with the red fluorescent dye PKH26 and injected into the liver of severe combined immunodeficiency mice. After 3 or 12 weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly single cells that were well integrated into the liver tissue. Human albumin was found in 8 of 11 animals by immunohistochemistry, and human albumin mRNA was detected in 4 of 10 host livers. The mechanism underlying this phenomenon seems to be transdifferentiation, because human and mouse albumin were found to be expressed in distinct cells in the host liver.

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