Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis.

Diane C Saunders
Marcela Brissova
Neil Phillips
Shristi Shrestha
John T Walker
Radhika Aramandla
Greg Poffenberger
David K Flaherty
Kevin P Weller
Julie Pelletier
Tracy Cooper
Matt T Goff
John Virostko
Alena Shostak
E Danielle Dean
Dale L Greiner
Leonard D. Shultz, The Jackson Laboratory
Nripesh Prasad
Shawn E Levy
Robert H Carnahan
Chunhua Dai
Jean Sévigny
Alvin C Powers

Abstract

Identification of cell-surface markers specific to human pancreatic β cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human β cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet β cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human β cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human β cells. Thus, NTPDase3 is a cell-surface biomarker of adult human β cells, and the antibody directed to this protein should be a useful new reagent for β cell sorting, in vivo imaging, and targeting.