Biomedical research

Mathematical Modelling and Simulation

Physics research

In vitro characterization and in vitro/in vivo simulation of the effect of hypoxia and drug dosis in glioblastoma growth. 
PGC2018-097257- B-C31. 
Acrónimo: GBM_SIMUL

Programme: Knowledge R&D projects and R&D Projects Research Challenges
Project start: 01/01/2019
Project end:   31/12/2021

In this subproject the in vitro and in silico study of the glioblastoma multiforme (GBM) tumor is proposed in the context exposed in the overall coordinated project. This tumor shows the main features of a rapid progression and multifactorial nature: its behavior attends to different stimuli present in the tumor environment. The first characteristic impacts on its mortality, and hence its importance in research. The later involves the analysis in the lab of a huge amount of cases and different conditions in order to understand its behavior. In this subproject 2 different available methodologies, although complementary, will be of application to the study of GBM: (i) study in vitro through microfluidic platforms and (ii) predictive simulation in silico.

Lab assays will be performed by means of automatized microfluidic platforms. Microfluidic chips are a class of enabling technology that substitutes classical assays over Petri dishes. This technology is especially relevant when a 3D structure is needed as well as to recreate a similar environment as the in vivo one, including the supply of nutrients, oxygen or drugs provision. On the other hand, it is foreseen in this subproject the study of different cases and situations. For this purpose, it is proposed the automatization of the microfluidic platform as well as the lab tests. Both the fabrication of the microfluidic chips as well as the design and fabrication of the automatized platform for testing are classified within the objectives and deliverables of the present subproject. Likewise, lab testing and results acquisition and interpretation will be carried out in this subproject. Specifically, it is considered the development of in vitro models including cyclic hypoxia and different doses of temozolamida on cell line U-251 of GBM. These results will be of application in one hand for the analysis of the behavior of GBM under different conditions. On the other hand, these results will be the basis for the calibration and validation of the models and simulations planned both in this subproject and the rest of subprojects.

Another fundamental objective of this subproject is dedicated to the development of continuum models which allow reproducing, understanding and explaining the observed behavior of the in vitro assays. Specifically, these models will include proliferation, death and migration terms due to mechanotaxis and chemotaxis, diffusion of substances (drugs, oxygen, nutrients); as well as the mechanical interaction with the substrate. The evolution of the cellular phenotype will be included through the concept of internal variables, which will describe the state of a cell population and its evolution along time. The numerical implementation of these models, computer simulation of the in vitro assays and their validation will allow: (i) advance in the knowledge and understanding of GBM through its mathematical description, (ii) development of a software product available for lab test planning, drug testing and support to the oncologist and basic researcher. This achievement may reduce lab testing and to shorten time/costs in the development of new drugs and protocols in the clinical treatment of GBM tumors.