University of Twente Student Theses


Vascularized bone marrow model for studying a breast tumour to bone metastasis using a multi-organ-on-a-chip approach.

Stevers, S.T. (2021) Vascularized bone marrow model for studying a breast tumour to bone metastasis using a multi-organ-on-a-chip approach.

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Abstract:Cancer has a growing incidence worldwide and metastases represent the primary cause of death from cancer. However, there is still a lot unknown about the mechanisms that support metastasis to specific organs. Bone marrow is one of the most frequently metastasized sites for different types of cancer such as, beast and prostate cancer. Therefore, a lot of research is performed into the understanding, prevention and treatment of the metastasis. To this end, in this work, a bonemarrowonchip is developed that can be connected with a vascular circulation to a tumour tissue. The development of a representative bone marrow tissue on chip is presented to actually be used for mimicking metastasis to bone marrow. First the hydrogel is investigated to form a bone vascularized tissue. To do so, the amount of self organization and migration of cells cultured as spheroids in the hydrogels is analyzed. Both Collagen I and Fibrin hydrogel are used, and from these two Fibrin hydrogel showed the best potential for vascularization of the spheroids. Next, the spheroid composition is structured considering bone marrow derived mesenchymal stem cells (MSCs), osteoblasts (OBs) and endothelial cells (ECs) of two types. First, the spheroids are formed in round bottom microwells and after two days injected into the hydrogel. Now the spheroids are cultured for 7 days in well plates during and after which various analysis methods are used to analyze the effect of different conditions. These analyses include quantification of the migration of cells in the hydrogel, immunostaining and quantitative polymerase chain reaction (qPCR). MSCs are combined with HUVECs to improve the vascularization of the tissue and with OBs to form a more representative bone marrow. Also, the effect of bone marrow endothelial cells (BMECs) on both MSCs and OBs is investigated to see the effect of the tissue specific ECs. In the end a triple culture of MSCs, OBs and BMECs was identified as the best cellular composition for the vascularized bone marrow formation. After the experiments with spheroids in wells plates, the best conditions are selected to be performed on chip. The on chip cultures however did not show the same results as the wells plate cultures. As of now there is no clear reason why but this has to be investigated further. Also, the qPCR has to be performed again to obtain more data points and control measurements from the different conditions.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Programme:Biomedical Engineering MSc (66226)
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