Engineering tolerance into transplanted beta cell lines.
In this paper we explore the possibility of improving, by genetic engineering, the resistance of insulin-secreting cells to the metabolic and inflammatory stresses that are anticipated to limit their function and survival when encapsulated and transplanted in a type 1 diabetic environment. We show that transfer of the Bcl-2 antiapoptotic gene, and of genes specifically interfering with cytokine intracellular signaling pathways, greatly improves resistance of the cells to metabolic limitations and inflammatory stresses.
Thorens
B
B
Institute of Pharmacology and Toxicology, University of Lausanne, Switzerland. Bernard.Thorens@ipharm.unil.ch
Dupraz
P
P
Cottet
S
S
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D019254:Genes, bcl-2; D005818:Genetic Engineering; D007108:Immune Tolerance / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma