Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK.

Journal of Biomedical Science
Hsiao-Yun LinShih-Chieh Hung

Abstract

Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs) offer renewable cells for generating insulin-producing cells (IPCs). We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation. Here, we report adding extracellular matrix proteins (ECM) such as fibronectin (FN) or laminin (LAM) enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor), PD98059 (MEK specific inhibitor) or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM. These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through a...Continue Reading

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Citations

Jan 4, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Marta PokrywczynskaTomasz Drewa
Jun 2, 2012·The Journal of Biological Chemistry·Hong QianMikael Sigvardsson
Feb 4, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Xiaozhen LiuFan He
Apr 20, 2011·Biochemical and Biophysical Research Communications·Jung-Pan WangShih-Chieh Hung
Jun 29, 2011·Journal of Tissue Engineering and Regenerative Medicine·Juan A MonteroJuan M Hurlé
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Aug 6, 2016·Seminars in Cancer Biology·Yan QinFrédéric Hollande
Jan 12, 2019·Tissue Engineering. Part C, Methods·Elahe HadaviAart van Apeldoorn
Feb 13, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Reyhaneh Nassiri MansourSeyed Ehsan Enderami
Dec 2, 2017·Biotechnology Journal·Ahmed Abdal DayemSsang-Goo Cho
Jun 18, 2020·Frontiers in Bioengineering and Biotechnology·Gabriel Romero LiguoriMartin Conrad Harmsen
Aug 23, 2020·International Journal of Molecular Sciences·Hui HuangSha Jin
Apr 13, 2021·Endocrine Reviews·John T WalkerAlvin C Powers

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Methods Mentioned

BETA
PCR
electrophoresis
enzyme-linked immunosorption assay
transfection
ELISA

Software Mentioned

LightCycler Relative Quantification

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