Purpose <p>Human-induced pluripotent stem cells (iPSCs) have the potential to differentiate into cells of various organs. Hepatocytes derived from iPSCs (i-Heps) have attracted much attention as an alternative treatment for liver transplantation in patients with liver failure. However, it is challenging to create sufficient i-Heps for clinical treatment, highlighting the need to develop an easier and more efficient culture method. In this study, we examined the effect of quiescent iPSC-derived stellate cells (i-Stes) on i-Hep proliferation.</p> Methods <p>i-Stes and i-Heps were differentiated from iPSCs.</p> Results <p>i-Stes expressed higher levels of hepatocyte growth factor (HGF) than the human hepatic stellate cell line LX-2. In addition, quiescent i-Sted promoted i-Hep proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway in i-Heps, which was impaired by the activation of i-Sted with transforming growth factor beta.</p> Conclusion <p>This study provides evidence that i-Sted can effectively induce i-Hep proliferation through HGF activation of the MAPK signaling pathway. Quiescent—but not activated—i-Stes may contribute to the creation of large numbers of i-Heps.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Induced pluripotent stem cell-derived stellate cells promote proliferation of induced pluripotent stem cell-derived hepatocytes through the mitogen-activated protein kinase pathway via hepatocyte growth factor

  • Takahiro Tomiyama,
  • Kazuki Takeishi,
  • Shinji Itoh,
  • Katsuya Toshida,
  • Norifumi Iseda,
  • Yuki Nakayama,
  • Takuma Ishikawa,
  • Takashi Motomura,
  • Takeshi Kurihara,
  • Takeo Toshima,
  • Rodrigo M. Florentino,
  • Alejandro Soto-Gutierrez,
  • Tomoharu Yoshizumi

摘要

Purpose

Human-induced pluripotent stem cells (iPSCs) have the potential to differentiate into cells of various organs. Hepatocytes derived from iPSCs (i-Heps) have attracted much attention as an alternative treatment for liver transplantation in patients with liver failure. However, it is challenging to create sufficient i-Heps for clinical treatment, highlighting the need to develop an easier and more efficient culture method. In this study, we examined the effect of quiescent iPSC-derived stellate cells (i-Stes) on i-Hep proliferation.

Methods

i-Stes and i-Heps were differentiated from iPSCs.

Results

i-Stes expressed higher levels of hepatocyte growth factor (HGF) than the human hepatic stellate cell line LX-2. In addition, quiescent i-Sted promoted i-Hep proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway in i-Heps, which was impaired by the activation of i-Sted with transforming growth factor beta.

Conclusion

This study provides evidence that i-Sted can effectively induce i-Hep proliferation through HGF activation of the MAPK signaling pathway. Quiescent—but not activated—i-Stes may contribute to the creation of large numbers of i-Heps.