Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK
<p>Abstract</p> <p>Background</p> <p>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-p...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-07-01
|
| Series: | Journal of Biomedical Science |
| Online Access: | http://www.jbiomedsci.com/content/17/1/56 |
| _version_ | 1818209081243992064 |
|---|---|
| author | Chiou Shih-Hwa Chen Ling-Lan Tsai Chih-Chien Lin Hsiao-Yun Wang Yng-Jiin Hung Shih-Chieh |
| author_facet | Chiou Shih-Hwa Chen Ling-Lan Tsai Chih-Chien Lin Hsiao-Yun Wang Yng-Jiin Hung Shih-Chieh |
| author_sort | Chiou Shih-Hwa |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-12T04:55:02Z |
| format | Article |
| id | doaj.art-2723820c66d047afa7eb51531f4c1b3e |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-12T04:55:02Z |
| publishDate | 2010-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-2723820c66d047afa7eb51531f4c1b3e2022-12-22T00:37:23ZengBMCJournal of Biomedical Science1021-77701423-01272010-07-011715610.1186/1423-0127-17-56Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERKChiou Shih-HwaChen Ling-LanTsai Chih-ChienLin Hsiao-YunWang Yng-JiinHung Shih-Chieh<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.jbiomedsci.com/content/17/1/56 |
| spellingShingle | Chiou Shih-Hwa Chen Ling-Lan Tsai Chih-Chien Lin Hsiao-Yun 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 Journal of Biomedical Science |
| 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 |
| url | http://www.jbiomedsci.com/content/17/1/56 |
| work_keys_str_mv | AT chioushihhwa fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk AT chenlinglan fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk AT tsaichihchien fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk AT linhsiaoyun fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk AT wangyngjiin fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk AT hungshihchieh fibronectinandlamininpromotedifferentiationofhumanmesenchymalstemcellsintoinsulinproducingcellsthroughactivatingaktanderk |