Ductular reaction-on-a-chip

Microfluidic co-cultures to study stem cell fate selection during liver injury

Amranul Haque, Pantea Gheibi, Gulnaz Stybayeva, Yandong Gao, Natalia J Torok, Alexander Revzin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Liver injury modulates local microenvironment, triggering production of signals that instruct stem cell fate choices. In this study, we employed a microfluidic co-culture system to recreate important interactions in the liver stem cell niche, those between adult hepatocytes and liver progenitor cells (LPCs). We demonstrate that pluripotent stem cell-derived LPCs choose hepatic fate when cultured next to healthy hepatocytes but begin biliary differentiation program when co-cultured with injured hepatocytes. We connect this fate selection to skewing in production of hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β1 caused by injury. Significantly, biliary fate selection of LPCs was not observed in the absence of hepatocytes nor did it happen in the presence of TGF-β inhibitors. Our study demonstrates that microfluidic culture systems may offer an interesting new tool for dissecting cellular interactions leading to aberrant stem cell differentiation during injury.

Original languageEnglish (US)
Article number36077
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 31 2016

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Microfluidics
Coculture Techniques
Stem Cells
Hepatocytes
Liver
Wounds and Injuries
Transforming Growth Factors
Stem Cell Niche
Growth Inhibitors
Pluripotent Stem Cells
Hepatocyte Growth Factor
Cell Differentiation

ASJC Scopus subject areas

  • General

Cite this

Ductular reaction-on-a-chip : Microfluidic co-cultures to study stem cell fate selection during liver injury. / Haque, Amranul; Gheibi, Pantea; Stybayeva, Gulnaz; Gao, Yandong; Torok, Natalia J; Revzin, Alexander.

In: Scientific Reports, Vol. 6, 36077, 31.10.2016.

Research output: Contribution to journalArticle

Haque, Amranul ; Gheibi, Pantea ; Stybayeva, Gulnaz ; Gao, Yandong ; Torok, Natalia J ; Revzin, Alexander. / Ductular reaction-on-a-chip : Microfluidic co-cultures to study stem cell fate selection during liver injury. In: Scientific Reports. 2016 ; Vol. 6.
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