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Simulation, Design and Fabrication of Microfluidic Systems for the Enrichment of Cancer Stem Cells and the Pharmacological Tests

Barisam Haghiri, Maryam | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 54817 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Saeedi, Mohammad Saeed; Kashaninejad, Navid; Trung Nguyen, Nam
  7. Abstract:
  8. Cancer is one of the leading causes of death worldwide, and despite all the advances in medical science, there isn't any definitive cure for it, yet. Researchers have recently considered the presence of cancer stem cells with the capability of tumorigenesis, invasion, metastasis, self-renewal, etc. as the main cause of inefficiency of cancer treatment. It means current therapies are able to kill the tumor mass, but they are not successful in confront of cancer stem cells and this causes the disease to recur a while after the apparent recovery. To study these specific cells, in this project, first the population of cancer stem-like cells was increased in the cancer cell mass, in other words, cancer stem-like cells were enriched in the sample, and then the drug efficacy was evaluated. For this purpose, a microfluidic system consisting of a channel with arrays of U-shaped barriers to trap cells and form cancerous multicellular spheroids was designed, simulated, and constructed. Then, by controlling the shear stress and oxygen and glucose concentrations previously estimated by numerical simulations, the enrichment of these rare cells was performed. In this study, A549 lung cancer cells were used. This designed microfluidic system was able to produce cellular aggregates in relatively uniform size and shape. The results showed that the anoikis phenomenon or lack of adhesion to the substrate as well as increasing glucose concentration and increasing shear stress enhances the population of cancer stem-like cells. Reducing the concentration of oxygen and glucose in such a way that it creates quiescent areas inside the aggregates, enriches the cancer stem-like cells. In this study, the effect of the enrichment method, i.e., shear stress and oxygen and glucose concentrations, on resistance to treatment with cisplatin was investigated. The results showed that a 23% decrease in oxygen concentration, a 350% increase in glucose and a 100% increase in shear stress caused a 1260, 750 and 830% increase in cisplatin chemoresistance, respectively. Therefore, it was concluded oxygen and glucose concentrations had the highest and the lowest effects on the therapeutic resistance of A549 cells, respectively. According to the results of the present study, by regulating the parameters affecting cell culture, effective enrichment of cancer stem cells can be achieved. Such studies can be used to understand the behavior of cancer cells, especially cancer stem cells, and to develop targeted therapies
  9. Keywords:
  10. Hypoxia ; Drug Delivery ; Microfluidic System ; Cell Enrichment ; Cancer Stem Cells

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