Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells

Philip Roelandt, Karen Ann Pauwelyn, Pau Sancho-Bru, Kartik Subramanian, Bipasha Bose, Laura Ordovas, Kim Vanuytsel, Martine Geraerts, Meri Firpo, Rita de Vos, Johan Fevery, Frederik Nevens, Wei Shou Hu, Catherine M. Verfaillie

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes. Remarkably, the same protocol can also differentiate rat multipotent adult progenitor cells (rMAPCs) to hepatocyte-like cells, even though rMAPC are isolated clonally from cultured rat bone marrow (BM) and have characteristics of primitive endoderm cells. A fraction of rMAPCs can be fated to cells expressing genes consistent with a PS/ME/DE phenotype, preceding the acquisition of phenotypic and functional characteristics of hepatocytes. Although the hepatocyte-like progeny derived from both cell types is mixed, between 10-20% of cells are developmentally consistent with late fetal hepatocytes that have attained synthetic, storage and detoxifying functions near those of adult hepatocytes. This differentiation protocol will be useful for generating hepatocyte-like cells from rodent and human stem cells, and to gain insight into the early stages of liver development.

Original languageEnglish (US)
Article numbere12101
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - 2010

Fingerprint Dive into the research topics of 'Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells'. Together they form a unique fingerprint.

Cite this