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

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 di...

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Autores principales: Lin, Hsiao-Yun, Tsai, Chih-Chien, Chen, Ling-Lan, Chiou, Shih-Hwa, Wang, Yng-Jiin, Hung, Shih-Chieh
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915967/
https://www.ncbi.nlm.nih.gov/pubmed/20624296
http://dx.doi.org/10.1186/1423-0127-17-56
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author Lin, Hsiao-Yun
Tsai, Chih-Chien
Chen, Ling-Lan
Chiou, Shih-Hwa
Wang, Yng-Jiin
Hung, Shih-Chieh
author_facet Lin, Hsiao-Yun
Tsai, Chih-Chien
Chen, Ling-Lan
Chiou, Shih-Hwa
Wang, Yng-Jiin
Hung, Shih-Chieh
author_sort Lin, Hsiao-Yun
collection PubMed
description 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.
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spelling pubmed-29159672010-08-05 Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK Lin, Hsiao-Yun Tsai, Chih-Chien Chen, Ling-Lan Chiou, Shih-Hwa Wang, Yng-Jiin Hung, Shih-Chieh J Biomed Sci Research 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. BioMed Central 2010-07-12 /pmc/articles/PMC2915967/ /pubmed/20624296 http://dx.doi.org/10.1186/1423-0127-17-56 Text en Copyright ©2010 Lin et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lin, Hsiao-Yun
Tsai, Chih-Chien
Chen, Ling-Lan
Chiou, Shih-Hwa
Wang, Yng-Jiin
Hung, Shih-Chieh
Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title_full Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title_fullStr Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title_full_unstemmed Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title_short Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
title_sort fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating akt and erk
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915967/
https://www.ncbi.nlm.nih.gov/pubmed/20624296
http://dx.doi.org/10.1186/1423-0127-17-56
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