PAX4 Promotes PDX1-induced Differentiation of Mesenchymal Stem Cells into Insulin-secreting Cells

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2017 Apr 8

PMID 28386318

Citations 12

Authors

Lifa Xu

Congjing Xu

Shuping Zhou

Xueke Liu

Jian Wang

Xinkuang Liu

Suping Qian

Yingru Xin

Yi Gao

Yongqiang Zhu

Xiaolong Tang

Affiliations

Soon will be listed here.

Abstract

A shortage of postmortem pancreatic tissue for islet isolation impedes the application of cell replacement therapy in patients with diabetes. As an alternative for islet cell transplantation, transcription factors, including PDX1, PAX4, and neurogenin-3, that aid in the formation of insulin-producing β cells during development have been investigated. The present study evaluated the effects of PAX4 and PDX1 on the differentiation of mesenchymal stem cells (MSCs) into insulin-producing β-like cells using recombinant adenoviruses carrying PDX1 or PDX1 plus PAX4. RT-PCR, Western blot, and immunofluorescence assays were used to detect the expression levels of relevant genes and proteins, and enzyme-linked immunosorbent assays were used to determine the amount of insulin and C-peptide secreted by the virus-infected cells following stimulation with high glucose. The results showed that PAX4 markedly enhanced the propensity of PDX1-positive MSCs to form mature islet-like clusters and functional insulin-producing β-like cells. Our findings provide a novel foundation for generating β-like cells from MSCs with PAX4 and PDX1 for future clinical application.

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