Human liver spheroid cultures in microfluidic chip co-cultures and comparative MetID studies

Visa enkel post
dc.contributor.authorAsserlind, Johanna
dc.contributor.departmentChalmers tekniska högskola / Institutionen för fysik (Chalmers)sv
dc.contributor.departmentChalmers University of Technology / Department of Physics (Chalmers)en
dc.date.accessioned2019-07-03T14:41:40Z
dc.date.available2019-07-03T14:41:40Z
dc.date.issued2017
dc.description.abstractThe liver is the most important site of drug metabolism in the human body. During drug development, it is therefore of high importance to employ a robust in vitro model that resembles the in vivo microenvironment, and is able to accurately predict the metabolism and disposition of compounds. This thesis is divided into two major parts. First, the metabolism of a set of compounds was characterized qualitatively in spheroids made from primary human hepatocytes (PHH), and the resulting data was compared to previous data from hepatocyte suspension culture and human in vivo data. The metabolites formed during a 72 hour incubation period was analyzed by LC-MS. Second, a co-culture between human liver spheroids, made from HepaRG cells and primary hepatic stellate cells, and primary human pancreatic islets in microfluidic 2-organ-chips was established, and the liver spheroids were functionally characterized. A total of 5 chip experiments were performed, where each chip experiment lasted for 7 days, and different conditions such as medium composition where examined. Various staining techniques and measurements of secreted albumin and LDH were used to assess long-term sustainability, function and viability of the spheroids. Some of the metabolites seen in humans were also formed in PHH spheroids, but the spheroid model was not able to fully predict the human in vivo metabolism. Spheroids were not shown to be a significantly better model to use compared to suspension cultures during these experiments. CYP activity analysis showed that decreasing metabolic function after a change in medium composition might be a factor. HepaRG spheroids were able to display several liver-like functions when cultured in the multi-organ chips, but the large size of the spheroids led to the formation of necrotic cores. Overall, while certain parameters need to be improved, the liver spheroids are promising models for studying several different aspects of liver functions as well as for establishing organ system models.
dc.identifier.urihttps://hdl.handle.net/20.500.12380/254292
dc.language.isoeng
dc.setspec.uppsokPhysicsChemistryMaths
dc.subjectBuilding Futures
dc.subjectEnergi
dc.subjectGrundläggande vetenskaper
dc.subjectHållbar utveckling
dc.subjectInnovation och entreprenörskap (nyttiggörande)
dc.subjectAnnan humaniora
dc.subjectBuilding Futures
dc.subjectEnergy
dc.subjectBasic Sciences
dc.subjectSustainable Development
dc.subjectInnovation & Entrepreneurship
dc.subjectOther Humanities
dc.titleHuman liver spheroid cultures in microfluidic chip co-cultures and comparative MetID studies
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster Thesisen
dc.type.uppsokH
local.programmeBiotechnology (MPBIO), MSc
Ladda ner
Original bundle
Visar 1 - 1 av 1
Bild (thumbnail)
Namn:
254292.pdf
Storlek:
21.64 MB
Format:
Adobe Portable Document Format
Beskrivning:
Fulltext
Ladda ner
Samling
Examensarbeten för masterexamen