Transduction of non-dividing adult human pancreatic beta cells by an integrating lentiviral vector

Q. Ju, D. Edelstein, M. D. Brendel, D. Brandhorst, H. Brandhorst, R. G. Bretzel, M. Brownlee

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Pancreatic islet cells are terminally differentiated endocrine cells and are refractory to stable infection by retroviral vectors, which require the breakdown of the nuclear membrane during cell division in order to insert the transgene into the host cell genome. Thus, attempts to render beta-cell allografts less immunogenic have had to rely on stable transfection of surrogate cells. Similarly, this problem has precluded the development of conditionally immortalized human beta cells for clinical allotransplantation. In this report, we demonstrate that adult human islet beta cells can be transduced by a new three-plasmid integrating lentiviral vector with an efficiency of 62 ± 1.8% at a multiplicity of infection (MOI) of 2.5 in vitro. This work makes genetic engineering of adult human pancreatic beta cells possible for the first time, allowing strategies to render beta-cell allografts non-immunogenic to be optimized and to creating conditionally immortalized human beta cells for clinical transplantation.

Original languageEnglish (US)
Pages (from-to)736-739
Number of pages4
JournalDiabetologia
Volume41
Issue number6
DOIs
StatePublished - Jun 18 1998

Keywords

  • Gene transfer
  • Human islet beta-cell
  • Lentiviral vector
  • Retrovirus
  • Transplantation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Ju, Q., Edelstein, D., Brendel, M. D., Brandhorst, D., Brandhorst, H., Bretzel, R. G., & Brownlee, M. (1998). Transduction of non-dividing adult human pancreatic beta cells by an integrating lentiviral vector. Diabetologia, 41(6), 736-739. https://doi.org/10.1007/s001250050977