TRANSDUCTION OF NONDIVIDING ADULT HUMAN PANCREATIC BETA-CELLS BY AN INTEGRATING LENTIVIRAL VECTOR

Pancreatic islet cells are terminally differentiated endocrine cells a nd are refractory to stable infection by retroviral vectors, which req uire the breakdown of the nuclear membrane during cell division in ord er to insert the transgene into the host cell genome. Thus, attempts t o render beta-cell allografts less immunogenic have had to rely on sta ble transfection of surrogate cells. Similarly, this problem has precl uded the development of conditionally immortalized human beta cells fo r clinical allotransplantation. In this report, we demonstrate that ad ult human islet beta cells can be transduced by a new three-plasmid in tegrating lentiviral vector with nn efficiency nf 62 +/- 1.8% at a mul tiplicity of infection (MOI) of 2.5 in vitro. This work makes genetic engineering of adult human pancreatic beta cells possible for the firs t time, allowing strategies to render beta-cell allografts non-immunog enic to be optimized and to creating conditionally immortalized human beta cells for clinical transplantation.