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Optimizing transduction of pig islet cell clusters for xenotransplantation

Optimizing transduction of pig islet cell clusters for xenotransplantation To the Editor: Pig neonatal islet cell clusters (NICC) are an attractive source of insulin‐producing tissue for potential transplantation into diabetic humans. As such, there is considerable interest in the modification of NICC to preserve the initial graft mass, and to prevent acute and chronic xenograft rejection whilst maintaining systemic immunity (reviewed [ 1 ]). This will almost certainly require the introduction of multiple molecules. Transgenic NICC that are protected from hyperacute, acute and even chronic rejection could then be safely transplanted into humans. Viral modification provides a surrogate way to determine which cytoprotective and immunomodulatory molecules should be used to generate transgenic pigs. Studies optimizing virally induced modifications of NICC in the context of xenotransplantation are limited. Previously, we have demonstrated that the ubiquitous CMV and EF1α promoters drive efficient gene expression in NICC after adenovirus (Adv) delivery [ 2 ]. In our hands, packaging of Adv is inefficient when inserts >8 kb are introduced. This limits the number of genes that Adv vectors can encode, so transduction with several viruses may be necessary to introduce multiple genes. We have now further optimized the introduction of several Adv vectors into NICC. What was the best time to http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

Optimizing transduction of pig islet cell clusters for xenotransplantation

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References (8)

Publisher
Wiley
Copyright
© 2009 John Wiley & Sons A/S
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1111/j.1399-3089.2009.00511.x
pmid
19243560
Publisher site
See Article on Publisher Site

Abstract

To the Editor: Pig neonatal islet cell clusters (NICC) are an attractive source of insulin‐producing tissue for potential transplantation into diabetic humans. As such, there is considerable interest in the modification of NICC to preserve the initial graft mass, and to prevent acute and chronic xenograft rejection whilst maintaining systemic immunity (reviewed [ 1 ]). This will almost certainly require the introduction of multiple molecules. Transgenic NICC that are protected from hyperacute, acute and even chronic rejection could then be safely transplanted into humans. Viral modification provides a surrogate way to determine which cytoprotective and immunomodulatory molecules should be used to generate transgenic pigs. Studies optimizing virally induced modifications of NICC in the context of xenotransplantation are limited. Previously, we have demonstrated that the ubiquitous CMV and EF1α promoters drive efficient gene expression in NICC after adenovirus (Adv) delivery [ 2 ]. In our hands, packaging of Adv is inefficient when inserts >8 kb are introduced. This limits the number of genes that Adv vectors can encode, so transduction with several viruses may be necessary to introduce multiple genes. We have now further optimized the introduction of several Adv vectors into NICC. What was the best time to

Journal

Xenotransplantation – Wiley

Published: Jan 1, 2009

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