title: PAX4 promotes PDX1-induced differentiation of mesenchymal stem cells into insulin-secreting cells.
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 cellsin vitrousing 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.
authors.affiliation: Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Lifa
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Respiration, Tumour Hospital of Affiliated Huainan Oriental Hospital Group, Anhui University of Science and Technology Huainan 232035, P.R. China.
authors.forename: Congjing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Xueke
authors.initials: X
authors.lastname: Liu
authors.affiliation: Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Xinkuang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Respiration, Tumour Hospital of Affiliated Huainan Oriental Hospital Group, Anhui University of Science and Technology Huainan 232035, P.R. China.
authors.forename: Suping
authors.initials: S
authors.lastname: Qian
authors.affiliation: Department of Respiration, Tumour Hospital of Affiliated Huainan Oriental Hospital Group, Anhui University of Science and Technology Huainan 232035, P.R. China.
authors.forename: Yingru
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, P.R. China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology Huainan 232001, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Tang
keywords: MSC; PAX4; PDX1; differentiation; pancreatic β cell