4.5 Article

Generation of Hepatocytes and Nonparenchymal Cell Codifferentiation System from Human-Induced Pluripotent Stem Cells

期刊

STEM CELLS INTERNATIONAL
卷 2022, 期 -, 页码 -

出版社

HINDAWI LTD
DOI: 10.1155/2022/3222427

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资金

  1. National Natural Science Foundation of China
  2. Natural Science Foundation of Guangdong Province
  3. Natural Science Foundation of Shenzhen City
  4. District Key Laboratory Fund of Longgang District of Shenzhen City
  5. Foundation of Beijing University of Chinese Medicine Department of Hepatopathy, Shenzhen Hospital
  6. [82172107]
  7. [2020A1515011314]
  8. [2021A1515011927]
  9. [2020B121206003]
  10. [JCYJ20190807101401682]
  11. [JCYJ20210324135014040]
  12. [LGKCZSYS2019000051]
  13. [2020-BUCMSZYLRC04]

向作者/读者索取更多资源

By including BMP4 in the hepatic differentiation medium, we have achieved co-differentiation of endoderm-derived hepatocytes and mesoderm-derived nonparenchymal cells, which has a beneficial effect on hepatocyte maturation and lifespan in vitro.
To date, hepatocytes derived from human-induced pluripotent stem cells (hiPSC) provide a potentially unlimited resource for clinical application and drug development. However, most hiPSC-derived hepatocyte-like cells initiated differentiation from highly purified definitive endoderm, which are insufficient to accurately replicate the complex regulation of signals among multiple cells and tissues during liver organogenesis, thereby displaying an immature phenotypic and short survival time in vitro. Here, we described a protocol to achieve codifferentiation of endoderm-derived hepatocytes and mesoderm-derived nonparenchymal cells by the inclusion of BMP4 into hepatic differentiation medium, which has a beneficial effect on the hepatocyte maturation and lifespan in vitro. Our codifferentiation system suggests the important role of nonparenchymal cells in liver organogenesis. Hopefully, these hepatocytes described here provide a promising approach in the therapy of liver diseases.

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