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

Hsiao-Yun Lin1,2†, Chih-Chien Tsai1,4†, Ling-Lan Chen1, Shih-Hwa Chiou1,3, Yng-Jiin Wang2* and Shih-Chieh Hung1,3,4*

Author Affiliations

1 Stem Cell Laboratory, Department of Medical Research and Education, Veterans General Hospital-Taipei, Taiwan

2 Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan

3 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

4 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

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Journal of Biomedical Science 2010, 17:56 doi:10.1186/1423-0127-17-56

Published: 12 July 2010

Abstract

Background

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).

Methods

We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.

Results

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.

Conclusions

These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.