Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function.

Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Research Abstract Details 

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Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Abstract Text:

Shane T Grey,Christopher Longo,Tala Shukri,Virendra I Patel,Eva Csizmadia,Soizic Daniel,Maria B Arvelo,Vaja Tchipashvili,Christiane Ferran,

Transplantation of an excessive number of islets of Langerhans (two to four pancreata per recipient) into patients with type I diabetes is required to restore euglycemia. Hypoxia, nutrient deprivation, local inflammation, and the beta cell inflammatory response (up-regulation of NF-kappaB-dependent genes such as inos) result in beta cell destruction in the early post-transplantation period. Genetic engineering of islets with anti-inflammatory and antiapoptotic genes may prevent beta cell loss and primary nonfunction. We have shown in vitro that A20 inhibits NF-kappaB activation in islets and protects from cytokine- and death receptor-mediated apoptosis. In vivo, protection of newly transplanted islets would reduce the number of islets required for successful transplantation. Transplantation of 500 B6/AF(1) mouse islets into syngeneic, diabetic recipients resulted in a cure rate of 100% within 5 days. Transplantation of 250 islets resulted in a cure rate of only 20%. Transplantation of 250 islets overexpressing A20 resulted in a cure rate of 75% with a mean time to cure of 5.2 days, comparable to that achieved with 500 islets. A20-expressing islets preserve functional beta cell mass and are protected from cell death. These data demonstrate that A20 is an ideal cytoprotective gene therapy candidate for islet transplantation.

Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Publishing Authors By Initials

ST Grey,C Longo,T Shukri,VI Patel,E Csizmadia,S Daniel,MB Arvelo,V Tchipashvili,C Ferran,

For similar proteins: recombinant proteins research abstracts see: proteins: recombinant proteins research

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Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 170

Page Numbers: 6250-6

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Jun

YEAR: 2003

Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Keywords Mesh Terms:

KEYWORDS: Recombinant Proteins

MESH TERMS: toxicity

Chemical & Substance for Abstract: Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. Information

Substance Name: TNFAIP3 protein, human

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function.

AFFILIATION: Immunobiology Research Center, Department of Surgery and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. sgrey@caregroup.harvard.edu

Country: United States

AGENCY: United States NIDDK

GRANT: R21DK062601

ACRONYM: DK

MEDLINETA: J Immunol

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