@article{b84dc0e0104544c389194c4aef23a11d,
title = "A strategy for the engineering of insulin producing cells with a broad spectrum of defense properties",
abstract = "Insulin-producing pancreatic beta cells are known to be extremely susceptible to the oxidative stress and hypoxia generated following islet transplantation in diabetic patients. We hereby present a novel in vivo selection strategy based on the isolation of insulin-producing cells with enhanced protection after repeated rounds of encapsulation and xenotransplantation. Rat insulinoma INS-1 cells were encapsulated in alginate macrobeads and transplanted in the peritoneal cavity of mice. After 2 days the beads were retrieved and cells were recovered from alginate and propagated in vitro until submitted to a second round of encapsulation and transplantation. Three days later, the surviving cells, named INS-1m2, were isolated from the alginate beads and their protection and functional activity examined. Compared to parental INS-1 cells, the selected INS-1m2 cells were more resistant to hydrogen peroxide, nitric oxide, alloxan and hypoxia. This enhanced protection of the selected cells correlated with the increased level of catalase and poly (ADP-ribose) polymerase expression. Although selected cells expressed more insulin than parental cells, no change in their insulin response to glucose was observed. We conclude that the in vivo selection strategy is a powerful tool for the engineering of insulin producing cells with a broad spectrum of defense properties.",
keywords = "Alginate encapsulation, Cell therapy, Diabetes, Insulinoma, Xenotransplantation",
author = "Konstantin Bloch and Olga Bloch and Igor Tarasenko and Daniel Lazard and Micha Rapoport and Pnina Vardi",
note = "Funding Information: This study was supported in part by grants from the Research Foundation of Tel Aviv University ( #1242401 ) and from the Israel Ministry of Science and Technology ( # 1244512 ). The authors thank Mrs. Sara Dominitz for her editorial assistance. ",
year = "2011",
month = mar,
doi = "10.1016/j.biomaterials.2010.11.018",
language = "אנגלית",
volume = "32",
pages = "1816--1825",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier Ltd.",
number = "7",
}