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

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. | Lin et al. Journal of Biomedical Science 2010 17 56 http content 17 1 56 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK 12 14 1 13 2 134 Hsiao-Yun Lin Chih-Chien Tsai Ling-Lan Chen Shih-Hwa Chiou Yng-Jiin Wang Shih-Chieh Hung 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. Background Type 1 diabetes caused by the autoimmune destruction of pancreatic p-cells is deficient in insulin and requires exogenous insulin for treatment. Islet transplantation offers a .