Studying the Interaction Between Macrophages and Glioblastoma Cells in 3D Brain Mimetic Hydrogels
Colucci Climent, Ana (2021)
Colucci Climent, Ana
2021
Master's Programme in Biomedical Technology
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Hyväksymispäivämäärä
2021-10-14
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202109207171
https://urn.fi/URN:NBN:fi:tuni-202109207171
Tiivistelmä
Glioblastoma Multiforme (GM) is the cause of the majority of brain tumour deaths worldwide. Cancer cells take advantage of the tumour microenvironment (TME) and the cells that com-prise it through complex signalling pathways in order to overcome our body’s immune re-sponse allowing them to grow and proliferate in our system. Even if this is known, tumour microenvironments and their signalling are yet not fully understood.
To approach this problem, the behaviour of glioblastoma cells together with macrophages was studied in a 3D brain mimetic hydrogel, created with either carbohydrazide conjugated dopamine-modified hyaluronic acid (HADA-CDH) or carbohydrazide conjugated hyaluronic acid (HA-CDH), combined with aldehyde functionalized chondroitin sulphate (CS-Ald), com-ponents that are present in the brain’s extracellular matrix. First, THP-1 and U87 MG cell lines were used as a model human macrophage cells and glioblastoma cells and were cul-tured together in the hydrogels to analyse their proliferation capabilities and gene expres-sions. After successfully establishing the protocol with the cell lines, we tested peripheral blood derived monocytes (PBMCs) derived macrophages and primary patient derived glioma cell (BT-13).
The results obtained during this study suggest that HA-CS hydrogels (HA-CDH combined with CS-Ald) sustained glioblastoma cells and macrophages better than HADA-CDH hydro-gels. Moreover, it was shown that this 3D in vitro model gave reliable results with THP-1 and U87 MG cell lines, where M2-type macrophages nourished glioblastoma growth and prolifer-ation. Nevertheless, the model did not show trustworthy enough results with the use of PBMC and BT-13 primary cells, therefore require further investigation.
Overall, this hydrogel platform opens a wide range of possible research areas and applica-tions, such as disease modelling combined with drug analyses and testing, or the use of nanoparticles to target and silence specific glioblastoma genes.
To approach this problem, the behaviour of glioblastoma cells together with macrophages was studied in a 3D brain mimetic hydrogel, created with either carbohydrazide conjugated dopamine-modified hyaluronic acid (HADA-CDH) or carbohydrazide conjugated hyaluronic acid (HA-CDH), combined with aldehyde functionalized chondroitin sulphate (CS-Ald), com-ponents that are present in the brain’s extracellular matrix. First, THP-1 and U87 MG cell lines were used as a model human macrophage cells and glioblastoma cells and were cul-tured together in the hydrogels to analyse their proliferation capabilities and gene expres-sions. After successfully establishing the protocol with the cell lines, we tested peripheral blood derived monocytes (PBMCs) derived macrophages and primary patient derived glioma cell (BT-13).
The results obtained during this study suggest that HA-CS hydrogels (HA-CDH combined with CS-Ald) sustained glioblastoma cells and macrophages better than HADA-CDH hydro-gels. Moreover, it was shown that this 3D in vitro model gave reliable results with THP-1 and U87 MG cell lines, where M2-type macrophages nourished glioblastoma growth and prolifer-ation. Nevertheless, the model did not show trustworthy enough results with the use of PBMC and BT-13 primary cells, therefore require further investigation.
Overall, this hydrogel platform opens a wide range of possible research areas and applica-tions, such as disease modelling combined with drug analyses and testing, or the use of nanoparticles to target and silence specific glioblastoma genes.