Promotion of mesenchymal-to-epithelial transition by rac1 inhibition with small molecules accelerates hepatic differentiation of mesenchymal stromal cells

Nan Yuan Teng, Yi Shiuan Liu, Hao Hsiang Wu, Yu An Liu, Jennifer H. Ho, Oscar Kuang Sheng Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

In vitro differentiation of stem cells into specific cell lineages provides a stable cell supply for cell therapy and tissue engineering. Therefore, understanding the mechanisms underlying such differentiation processes is critical for generating committed lineage-specific cell progenies effectively. We previously developed a two-step protocol to differentiate mesenchymal stromal cells (MSCs) into hepatocyte-like cells. Since hepatic differentiation involves mesenchymal-epithelial transition (MET), we hypothesize that promoting MET could further accelerate the differentiation process. Ras-related C3 botulinum toxin substrate 1 (Rac1) is involved in actin polymerization and its role in MET was investigated in the study. Our results showed that inhibition of Rac1 activation by Rac1-specific inhibitor, NSC23766, led to cells favoring epithelial morphology and being more packed during hepatic differentiation. In addition, Rac1 inhibition accelerated the upregulation of hepatic marker genes accompanied by more mature hepatic functions. Taken together, promotion of MET by inhibiting Rac1 accelerates the hepatic differentiation of MSCs. Our findings open a new prospect of directing the commitment of MSCs by manipulating cell morphology and cytoskeleton arrangement through small molecules. The results provide further insight into scaffold design for rapid production of MSC-differentiated hepatocytes.

Original languageEnglish
Pages (from-to)1444-1454
Number of pages11
JournalTissue Engineering - Part A
Volume21
Issue number7-8
DOIs
StatePublished - 01 04 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright 2015, Mary Ann Liebert, Inc. 2015.

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