title: Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury.
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.
authors: Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
authors: Amranul
authors: A
authors: Haque
authors: Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
authors: Pantea
authors: P
authors: Gheibi
authors: Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
authors: Gulnaz
authors: G
authors: Stybayeva
authors: Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
authors: Yandong
authors: Y
authors: Gao
authors: Department of Internal Medicine, University of California Davis, Sacramento, CA 95835, USA.
authors: Natalie
authors: N
authors: Torok
authors: Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
authors: Alexander
authors: A
authors: Revzin
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000633:toxicity*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism; D008099:Liver / Q000166:cytology; D051379:Mice; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin / Q000032:analysis; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D053552:Keratin-7; D012709:Serum Albumin; D053773:Transforming Growth Factor beta1; D000431:Ethanol; D017228:Hepatocyte Growth Factor