Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy
Abstract: Loss 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.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy ; day:07 ; month:11 ; year:2023 ; extent:20
EMBO molecular medicine / European Molecular Biology Organization ; (07.11.2023) (gesamt 20)
- Creator
- DOI
-
10.15252/emmm.202317928
- URN
-
urn:nbn:de:101:1-2023110714262794290329
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:46 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- So, Wing Yan
- Liao, Yilie
- Liu, Wai Nam
- Rutter, Guy
- Han, Weiping
Other Objects (12)
Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation
A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
Bioengineered Islet Cell Transplantation
Fetal islet transplantation : implications for diabetes
Islet transplantation: overcoming the organ shortage
Islet transplantation in type 1 diabetes : islet-expressed CXCL10 promotes graft rejection
The role of ferroptosis in islet transplantation
Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration
The Use of Biomaterials in Islet Transplantation
Further Analyses of Pancreas Islet Immunogenicity, a Major Barrier to Successful Islet Transplantation
Improvement of islet transplantation by the fusion of islet cells with functional blood vessels
Who Should Be Considered for Islet Transplantation Alone?
Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation
A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
Bioengineered Islet Cell Transplantation
Fetal islet transplantation : implications for diabetes
Islet transplantation: overcoming the organ shortage
Islet transplantation in type 1 diabetes : islet-expressed CXCL10 promotes graft rejection
The role of ferroptosis in islet transplantation
Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration
The Use of Biomaterials in Islet Transplantation
Further Analyses of Pancreas Islet Immunogenicity, a Major Barrier to Successful Islet Transplantation
Improvement of islet transplantation by the fusion of islet cells with functional blood vessels
Who Should Be Considered for Islet Transplantation Alone?
Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation
A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
Bioengineered Islet Cell Transplantation
Fetal islet transplantation : implications for diabetes
Islet transplantation: overcoming the organ shortage
Islet transplantation in type 1 diabetes : islet-expressed CXCL10 promotes graft rejection
The role of ferroptosis in islet transplantation
Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration
The Use of Biomaterials in Islet Transplantation
Further Analyses of Pancreas Islet Immunogenicity, a Major Barrier to Successful Islet Transplantation
Improvement of islet transplantation by the fusion of islet cells with functional blood vessels