The impact of human relevant mixture of contaminants on the development of human adipocytes

Sammanfattning: The objective of this project was to investigate how organic anthropogenic chemicals (OCs) effect the differentiation of adipocytes in the human body. The objective is also to contribute to novel research in how groups of chemicals in our surrounding affect us. The second objective of the project was to examine the exposure levels of the different compounds in the mixture during and after the differentiation of the stem cells. By setting up a method using GC-MS and spiking samples with a PCB/Pest mixture the retention time and optimal parameters could be determined.  Previous literature studies have resulted in a chemical mixture of the 50 most common OCs analyzed in human blood from the general population and are named the RiskMix chemicals. The RiskMix was prepared in a chemical mixture used to expose the human mesenchymal stem cells (hMSC) during a ten-day long adipogenesis model for the differentiation to adipocytes. The method used is a toxicological assay to determine how and if the hMSCs are affected by this chemical mixture in concentrations of 0.01 – 100 times human relevance.  During the differentiation of the hMSCs the chemical mixture was added in different dilutions and the results showed a significant difference in % adipocytes when exposed to the mixture of 100 times human relevance. However, the number of cells developed, meaning the total number of cells developed both to adipocytes and other cells, showed no significant difference. This means, that the total number of cells developed were not affected by the chemical mixture in the sake of toxicity. The recovery of each compound was calculated between 30-70% showing that the method needs further optimization for the compound with the lower recovery. The relative standard deviation - RSD was calculated to majorly below 20% and shows that the method was stable. The project concludes that chemicals in the RiskMix at 100 times the human relevance has an impact on the development of human adipocytes. However, future studies are required to fully understand which ones of these chemicals contribute to the adipogenic effect and if there is a combined effect of the compounds.