Development of a Hepatocyte Spheroid Culture Model for Drug Uptake, Metabolism and Transporter Studies

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dc.contributor.authorChouhan, Bhavik
dc.contributor.departmentChalmers tekniska högskola / Institutionen för teknisk fysiksv
dc.contributor.departmentChalmers University of Technology / Department of Applied Physicsen
dc.date.accessioned2019-07-03T13:49:48Z
dc.date.available2019-07-03T13:49:48Z
dc.date.issued2015
dc.description.abstractThe liver is a key organ in drug bioavailability including uptake, metabolism, and excretion as well as drug toxicity. Thus, a robust liver in vitro model that resembles in vivo micro environment with improved predictive capabilities is highly warranted. The focus in this thesis has been to develop and characterize a 3D liver spheroid model for the study of long-term drug uptake, metabolism, and transport. The bipotent progenitor cell line HepaRG has been used as it is known to express various liver specific markers and function in its differentiated state similar to primary human hepatocytes. Culturing these cells onto ultra-low attachment plates derived spheroid formation after 3 days independent of cellular concentration. Various staining techniques were used to investigate long-term sustainability of 2000 and 4000 cell spheroid culture. The gene expression analysis of the drug metabolizing cytochrome P450 (CYP) enzymes illustrated higher expression level in spheroid formation compared to 2D control while drug transporter, MRP2, hepatocyte markers Ki67, albumin, and CK19 all showed moderate to low expression. The HepaRG spheroid model showed promising results. The enzyme activity of CYP2C9, CYP2D6, and CYP3A4 was measurable throughout the whole cultivation period with a peak activity at day 7 while CYP1A2 showed no activity.
dc.identifier.urihttps://hdl.handle.net/20.500.12380/225710
dc.language.isoeng
dc.setspec.uppsokPhysicsChemistryMaths
dc.subjectGrundläggande vetenskaper
dc.subjectHållbar utveckling
dc.subjectInnovation och entreprenörskap (nyttiggörande)
dc.subjectFysik
dc.subjectBiologiska vetenskaper
dc.subjectBasic Sciences
dc.subjectSustainable Development
dc.subjectInnovation & Entrepreneurship
dc.subjectPhysical Sciences
dc.subjectBiological Sciences
dc.titleDevelopment of a Hepatocyte Spheroid Culture Model for Drug Uptake, Metabolism and Transporter Studies
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster Thesisen
dc.type.uppsokH
local.programmeBiotechnology (MPBIO), MSc
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