Meistaravörn verkfræðideild - Davíð Ingvi Snorrason
MSc í heilbrigðisverkfræði
- Time: January 17th
- Room: M104
- Student: Davíð Ingvi Snorrason
- Thesis Title: Describing the glucose-lactate consumption rate during adipogenic differentiation of adult human bone marrow derived stem cells: A premise to explore possible model prediction of enzyme activity.
- Supervisor: Ólafur Eysteinn Sigurjónsson, Professor at Reykjavik University, Óttar Rolfsson, Professor at University of Iceland and Sarah McGarrity post-doc.
- Examiner: Sigurður Brynjólfsson, Professor, University of Iceland.
Abstract
There is currently a lack of knowledge about the metabolic processes during adipogenic differentiation of mesenchymal stem cells. The process itself is extremely complex and sensitive to change. Expanding the knowledge of adipogenesis is of great value for the development of treatments for metabolic disease and regenerative medicine. Examining the changes in glucose uptake and lactate excretion by the MSCs, from four donors, during 21 day adipogenesis culture can indicate timepoints of interest in the process. Samples were taken from the MSC cell growth medium during expansion and adipogenesis. The samples were measured for Glucose, lactate, glutamine, glutamate and ammonia. The measured values, for day seven of adipogenesis, were then applied as constraints to the iMSC1255 metabolic model to generate a preliminary model for adipogenesis. Existing measurements from an osteogenesis process, for the same metabolites, were then used to constrain the iMSC1255 model. The flux values through each reaction in the adipogenesis and osteogenesis models were compared. The comparison was drawn using a Kolmogorov-Smirnov test to find statistically relevant differences. The reactions of most interest were reactions that requires specific enzyme activity to take place.
Two reactions showed the greatest difference between the adipogenesis and osteogenesis models.
The ACAT1 reaction showed for more activity in the adipogenesis model while the G6PDH1 reaction showed much greater activity in osteogenesis.
By constraining five metabolites in the iMSC1255 model using measured values from adipogenesis and osteogenesis it is possible to generate two separate models. The resulting models then describe statistically significant differences in reactions related to key enzymes.
These models and results are promising but need further study and verification.
Keywords: Mesenchymal stem cells, adipogenesis, osteogenesis, model, metabolomics, glucose, lactate, glutamine, glutamate, ammonia.
