{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:18:39Z","timestamp":1790518719807,"version":"4.1.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"3","funder":[{"name":"NIH","award":["DK107255"],"award-info":[{"award-number":["DK107255"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:p> A number of cell culture approaches have been described for maintenance of primary hepatocytes. Forming hepatocytes into three-dimensional (3-D) spheroids is one well-accepted method for extending epithelial phenotype of these cells. Our laboratory has previously observed enhanced function of two-dimensional (2-D, monolayer) hepatocyte cultures in microfluidic devices due to increased production of several hepato-inductive growth factors, including hepatocyte growth factor (HGF). In the present study, we wanted to test a hypothesis that culturing hepatocyte spheroids (3-D) in microfluidic devices will also result in enhanced phenotype and function. To test this hypothesis, we fabricated devices with small and large volumes. Both types of devices included a microstructured floor containing arrays of pyramidal wells to promote assembly of hepatocytes into spheroids with individual diameters of ~100 \u00b5m. The hepatocyte spheroids were found to be more functional, as evidenced by higher level of albumin synthesis, bile acid production, and hepatic enzyme expression, in low-volume compared with large-volume devices. Importantly, high functionality of spheroid cultures correlated with elevated levels of HGF secretion. Although decay of hepatic function (albumin secretion) was observed over the course 3 wk, this behavior could be abrogated by inhibiting TGF-\u03b21 signaling. With TGF-\u03b21 inhibitor, microfluidic hepatocyte spheroid cultures maintained high and stable levels of albumin synthesis over the course of 4 wk. To further highlight utility of this culture platform for liver disease modeling, we carried out alcohol injury experiments in microfluidic devices and tested protective effects of interleukin-22: a potential therapy for alcoholic hepatitis. <\/jats:p>","DOI":"10.1152\/ajpcell.00094.2020","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T18:58:05Z","timestamp":1595444285000},"page":"C552-C560","source":"Crossref","is-referenced-by-count":28,"title":["Microfluidic confinement enhances phenotype and function of hepatocyte spheroids"],"prefix":"10.1152","volume":"319","author":[{"given":"Jong Hoon","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Loarca","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, 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