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Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury SCIENTIFIC REPORTS Haque, A., Gheibi, P., Stybayeva, G., Gao, Y., Torok, N., Revzin, A. 2016; 6

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)-ß1 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-ß 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.

View details for DOI 10.1038/srep36077

View details for Web of Science ID 000386562400001

View details for PubMedID 27796316

View details for PubMedCentralID PMC5086854