Cell-based therapy is promising strategy for the cure of insulin deficient diabetes. One of such strategies, islet transplantation, has achieved remarkable success over the past decade, but its use is limited due to islet supply and graft survival. Another cell-based strategy is to regenerate the insulin-producing ?-cells from other cell types. In the preliminary studies, we explored a strategy to regenerate ?-cells from the neighboring glucagon-producing ?-cells in pancreatic islets. Specifically, we explored Pax4, a transcription factor critical for the determination of ?- vs ?-cell lineage during development, for this purpose. Our data showed Pax4 gene transfer into ?TC1.9 cells, a clonal ?-cell line, induced them to adopt ?-cell phenotype. We also found Pax4 gene transfer into primary human islets significantly improved ?-cell function, and had circumstantial evidence indicating Pax4 not only promoted ?-cell survival, but also induced ?-to-? cell conversion. Despite the extensive preliminary studies, more investigations are required in order to fully realize the therapeutic potential of Pax4 and to thoroughly understand its actions. We thus propose two specific aims in this project: 1) To investigate whether Pax4 gene transfer into donor human islets improves the therapeutic efficacy of islet transplantation; and 2) To investigate whether Pax4 induces ?-to-? cell conversion in primary islets and in vivo using lineage-tracing technology. Clearly, the project will provide important information regarding the therapeutic actions and potential of Pax4 for diabetes treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK107412-02
Application #
9304205
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Sato, Sheryl M
Project Start
2016-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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