Abstracts 6th International Congress of the Cell Transplant Society
Abstract:ENGINEERING A GLUCOSE-SENSITIVE INSULIN-PRODUCING HUMAN HEPATOCYTE CELL LINE FOR THE TEATMENT OF TYPE I DIABETES
Teru Okitsu,1 Naoya Kobayashi,1 Hee-Sook Jun,2 Seungjin Shin,2 Su-Jin Kim,2 Jaeseok Han,2 Toshinori Totsugawa,1 Karen Westerman,3 Noriaki Tanaka,1 Philippe Leboulch,3 and Ji-Won Yoon2
1Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan; 2Laboratory of Viral and Immunopathogenesis of Diabetes, The University of Calgary, Canada; 3Division of Health Sciences and Technology, Massachusetts Institute of Technology
Purpose: The expansion of the source for cell therapies to treat insulin-dependent diabetic patients is required to overcome the worldwide shortage of donor pancreata for islet transplantation. Toward this goal, we genetically modified human hepatocytes to secrete insulin in responding glucose levels.
Methods: First, human hepatocytes were reversibly immortalized using a retroviral gene transfer of human telomerase and Cre/loxP-mediated Cre/loxP recombination. Then, a plasmid expressing insulin under a hepatocyte-specific promoter was introduced into the cell line. A cell line was established and analyzed in the present study. Glucose-sensitive insulin secretion was examined at RNA and protein levels. The effect of in vivo transplantation was evaluated in a mouse model of diabetes induced by streptozocin (STZ).
Results: Expression and secretion of insulin was increased in the cell line when it was exposed to high glucose culture condition. Transplantation of the cell line into the subrenal capsule normalized blood glucose levels in STZ-treated diabetic mice, in contrast control diabetic mice showed continuous high levels of blood glucose. Interestingly, cell transplantation into normal nondiabetic mice did not induce hypoglycemia.
Conclusion: We have established a glucose-sensitive insulin-producing human hepatocyte cell line. The cell line would be a useful tool for diabetes-targeted cell therapies, such as cellular transplantation and bioartificial pancreata.
Document Type: Abstract
Publication date: January 1, 2003
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