Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- On the improvement of in vitro senescence studies by applying microfluidic technology and mathematical modelling(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-06-09) Rios Maciel, Mauricio Andrés; González Meljem, José Mario; puelquio; Álvarez, Mario Moisés; Trujillo de Santiago, Grissel; Escuela de Ingeniería y Ciencias; Campus MonterreyCellular senescence can be defined as an irreversible cell cycle arrest, which has been termed as an ‘antagonistic pleiotropy’ because of the duality of its role in aging. While the early-life on-set of the phenotype prevents tumorigenesis and plays an important part on the immune system-mediated removal of damaged cells, accumulation of senescent cells late in life is linked to the development of age-related diseases; thus, senescence is a target for anti-aging therapies. However, the senescent phenotype is very complex and heterogenous, making in vitro approaches desirable for the study of their individual components. In vitro culture of senescence presents a complex combination of different types of cells, including senescent, non-senescent, arrested and apoptotic, making it challenging to study the process in a complete manner. In addition, senescent cells have complex intercellular interactions, as well as ECM interactions. Recent approaches have used microfluidic technology alongside the incorporation of three-dimensional hydrogel-based matrixes to better mimic the microenvironment of the cell in vitro to make it more physiologically relevant. In this work we focus on the preliminary work for a further translation of traditional in vitro senescence techniques to a 3D and microfluidic environment. We assessed, analyzed and verified the behavior of endothelial HMEC-1 cells when cultured on GelMA-based hydrogel, as well as the effects of the matrix in senescence induction and assessment methods. We developed a mathematical model based on reported data to identify variables of importance and simulate the transition between states of proliferation, death and senescence through time in a senescent culture induced through doxorubicin. We observed that doxorubicin-induced senescence in endothelial cells stimulates apoptosis but yields an acceptable percentage of induction. After transferring these experiments to the GelMA-based hydrogel, neither induction nor assessment seemed to present a problem. We observed that endothelial cells in GelMA tend to adjust to a specific percentage, giving insight into the importance of the pore size in the matrix. Finally, the mathematical model shed light on the importance of time after treatment in the transition to senescent cells but also the turnover to dead population.