Microfluidic platforms to evaluate the effects of drugs on fertility and proteins on cancer progression – a focus on cisplatin, alpha-smooth muscle actin, and glial cell line-derived neurotrophic factor

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Bustillo Perez, Bexi
Microfluidics , Chemotherapy , Cancer , Organ-on-chip , Hydrogels
The introduction of in vitro systems that can mimic organ physiology and allow studying the progression of diseases such as cancer is necessary to get reliable information about cell responses and test drug efficacy and toxicity. Classical cell culture systems facilitate a wide range of clinical in vitro studies. These cell culture systems often consist of static and flat platforms that poorly mimic the conditions in living organisms. Microfluidics has emerged as an innovative technology that provides the tools to study cells in dynamic conditions that are present in the cell microenvironment. Two-dimensional (2D) and three-dimensional (3D) microfluidic cell cultures also referred to as organ-on-a-chip (OOC) have proved to have the potential to replace animal models since it is possible to recreate key factors of the organs inside the human body, those factors include gradients of growth factors, oxygen, pH, cycling strain, and shear stress. In the present work, microfluidic platforms have been designed and fabricated to seed and grow bovine oviduct epithelial cells, to measure changes in the cilia beating frequencies (CBFs), when those cells are exposed to cisplatin using an oviduct-on-chip platform. The transparent membrane assembled in this device facilitates observational studies of the cells alive. Establishing an air-liquid interface in the microfluidic chip allowed us to maintain the cell polarization for up to three months. An oviduct fimbriae-on-a-chip was also developed with the previously fabricated microfluidic device, to study some of the early events that occur in the development of ovarian cancer. A third microfluidic platform was fabricated to evaluate cell migration mediated by the Rearranged during transfection (RET) receptor and to evaluate the response of cells to chemotherapy in different collagen-based hydrogels.
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