- 作者: Hsiao-Yun Lin; Chih-Chien Tsai; Ling-Lan Chen; Shih-Hwa Chiou; Yng-Jiin Wang; Shih-Chieh Hung
- 作者服務機構: Stem Cell Laboratory, Department of Medical Research and Education, Veterans General Hospital-Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --