Dolaşımdaki tümör hücreleri araştırmalarında kullanılmak üzere sirkülasyonlu mikroakışkan biyoreaktörün tasarımı ve hemodinamik kayma gerilimi kuvvetlerinin meme kanseri (MDA-MB-231) hücre canlılığı üzerine etkisinin incelenmesi

Abstract

Circulating tumor cell model  This model is basically a mimic for the cellular microenvironment as the cell flows such as in hemodynamic circulation.  This work hints a unique direction that cancer cells lose their viability during circulating in flow.Figure A. Circulating microfluidic bioreactor and circulating tumor cell model Purpose: The purpose of the study is to design a broadly applicable experimental method to model hemodynamic biomechanical factors (fluid flow and shear stress) under well-controlled parameters and investigate how hemodynamic shear stress affects MDA-MB-231 breast cancer cell viability.Theory and Methods: In this study, a peristaltic circulating flow bioreactor is designed and applied to MDA-MB-231 breast cancer cells to mimic the fluid dynamics of hemodynamic circulation. For this purpose, we designed a bioreactor system to evaluate the effect of hemodynamic shear stress on a model system to represent the morphogenetic changes of MDA-MB-231 breast cancer cells as an in-vitro cancer bioreactor model. To mimic hemodynamic conditions, we first theoretically evaluated and characterized the physical environmental parameters such as shear stress and velocity profiles in order to assess and predict their influence on cancer cells in peristaltic flow culture. During the circulation culture, MDA-MB-231 breast cancer cell viability was determined with MTT and live/dead analyzes under various hemodynamic shear stresses (33, 49 and 66 dyn cm − 2 ) and circulation time (6, 12 and 24 h).Results: MTT test results on MDA-MB-231 cells showed that cell viability decreased as hemodynamic shear stress and circulation time increased compared to breast cancer cells cultured under static conditions attached to the surface. Significant reductions in cell viability of up to 20% occurred as increased hemodynamic shear stress (66 dyn cm − 2 ) and culture time (24 h) increased with flow rate. Conclusion:Our model is a simplified version of blood circulation, simulating fluid shear stresses in absence of other cellular components with this system, the viability of cancer cells under hemodynamic flow conditions can be evaluated. Also, this system allows exploring the unknowns in circulating tumor cell heterogeneity.