Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

EMBO Molecular Medicine

10.15252/emmm.202317928

http://dx.doi.org/10.15252/emmm.202317928

Wing Yan So, Yilie Liao, Wai Nam Liu, Guy A Rutter, Weiping Han

07 November 2023

So, W. Y., Liao, Y., Liu, W. N., Rutter, G. A., & Han, W. (2023). Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy. EMBO Molecular Medicine, 15(12). Portico. https://doi.org/10.15252/emmm.202317928

AbstractLoss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declined beta cell mass. Thus, strategies to preserve beta cells are imperatively needed. In this study, we identified paired box 6 (PAX6) as a critical regulator of beta cell survival. Under diabetic conditions, the human beta cell line EndoC‐βH1, db/db mouse and human islets displayed dampened insulin and incretin signalings and reduced beta cell survival, which were alleviated by PAX6 overexpression. Adeno‐associated virus (AAV)‐mediated PAX6 overexpression in beta cells of streptozotocin‐induced diabetic mice and db/db mice led to a sustained maintenance of glucose homeostasis. AAV‐PAX6 transduction in human islets reduced islet graft loss and improved glycemic control after transplantation into immunodeficient diabetic mice. Our study highlights a previously unappreciated role for PAX6 in beta cell survival and raises the possibility that ex vivo PAX6 gene transfer into islets prior to transplantation might enhance islet graft function and transplantation outcome.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: A*STAR
Grant Reference no. : Use-Inspired Basic Research Award

This research / project is supported by the A*STAR - A*STAR Strategic Research Program
Grant Reference no. : 21718

This research / project is supported by the National Medical Research Council - Open Fund - Young Individual Research Grant
Grant Reference no. : NMRC/OFYIRG/066/2018-00

https://oar.a-star.edu.sg/communities-collections/articles/20201

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Institute of Molecular and Cell Biology