Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation

Y. Clare Zhang, R. Damaris Milano, Antonello Pileggi, Matthew Powers, Jeffrey Cross, Clive Wasserfall, Marda Scott-Jorgensen, Martha Campbell-Thompson, James M. Crawford, Terence Flotte, Tamir M. Ellis, Camillo Ricordi, Mark A. Atkinson, Luca A Inverardi

Research output: Contribution to journalArticle

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Abstract

Previous studies suggest that therapeutic expression of interleukin (IL)-4 by islet cells improves their efficacy in transplantation models directed at reversing type 1 diabetes. We investigated the effects of introducing IL-4 into islets with recombinant adenoassociated virus (rAAV) on the reversal of hyperglycemia in a syngeneic marginal islet mass transplantation model. C57BL/6 islets were mock-transduced or transduced with rAAV expressing murine IL-4 (rAAV-IL-4) or rAAV expressing green fluorescent protein (rAAV-GFP) before transplantation of a marginal mass into diabetic mice. Normoglycemia was achieved in only 1/7 mice receiving rAAV-IL-4 transduced islets in comparison to 6/6 mock-transduced and 4/6 rAAV-GFP transduced animals. The failure of IL-4 expressing islets was not associated with cellular toxicity of rAAV or impairment of glucose-stimulated insulin release in vitro. Islet expression of IL-4 led to impaired metabolic function in mice receiving a marginal mass of syngeneic islets.

Original languageEnglish
Pages (from-to)1184-1186
Number of pages3
JournalTransplantation
Volume74
Issue number8
StatePublished - Oct 27 2002
Externally publishedYes

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Islets of Langerhans Transplantation
Dependovirus
Interleukin-4
Viruses
Transplantation
Green Fluorescent Proteins
Type 1 Diabetes Mellitus
Islets of Langerhans
Hyperglycemia
Insulin
Glucose

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Zhang, Y. C., Milano, R. D., Pileggi, A., Powers, M., Cross, J., Wasserfall, C., ... Inverardi, L. A. (2002). Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation. Transplantation, 74(8), 1184-1186.

Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation. / Zhang, Y. Clare; Milano, R. Damaris; Pileggi, Antonello; Powers, Matthew; Cross, Jeffrey; Wasserfall, Clive; Scott-Jorgensen, Marda; Campbell-Thompson, Martha; Crawford, James M.; Flotte, Terence; Ellis, Tamir M.; Ricordi, Camillo; Atkinson, Mark A.; Inverardi, Luca A.

In: Transplantation, Vol. 74, No. 8, 27.10.2002, p. 1184-1186.

Research output: Contribution to journalArticle

Zhang, YC, Milano, RD, Pileggi, A, Powers, M, Cross, J, Wasserfall, C, Scott-Jorgensen, M, Campbell-Thompson, M, Crawford, JM, Flotte, T, Ellis, TM, Ricordi, C, Atkinson, MA & Inverardi, LA 2002, 'Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation', Transplantation, vol. 74, no. 8, pp. 1184-1186.
Zhang, Y. Clare ; Milano, R. Damaris ; Pileggi, Antonello ; Powers, Matthew ; Cross, Jeffrey ; Wasserfall, Clive ; Scott-Jorgensen, Marda ; Campbell-Thompson, Martha ; Crawford, James M. ; Flotte, Terence ; Ellis, Tamir M. ; Ricordi, Camillo ; Atkinson, Mark A. ; Inverardi, Luca A. / Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation. In: Transplantation. 2002 ; Vol. 74, No. 8. pp. 1184-1186.
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