Finite element analysis of stem cells mechanical stimulations for differentiation into cardiomyocytes

M. Ebad, B. Vahidi
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Abstract

Heart failure is the leading cause of death in the world and there are still many flaws in its diagnosis. At present, surgical interventions for the treatment of cardiovascular disease are limited to the absence of organ donors for transplantation and the complications of immunosuppressive therapy. Researchers are looking for new ways to regenerate a damaged heart. Tissue engineering has emerged as a new technology using cells with regenerative capacity, scaffolds, and growth factors. Stem cells are optimal cell sources for cardiac tissue engineering due to their ability to self-repair and differentiation into cardiomyocytes. Since the cardiomyocytes inside the body are in a dynamic environment under cyclic strain and pulsatile flow due to the rhythmic heartbeat, these mechanical stimuli are important factors in differentiating stem cells, regulating cardiac tissue function, and homeostasis. This study aims to simulate the effect of pulsatile flow and cyclic strain exerted on a perfusion bioreactor on stem cells for cardiac tissue engineering applications (cardiomyocyte cells). Since shear stress activates transcription pathways, this parameter is very effective in the differentiation of stem cells to cardiomyocytes. The present study attempts to evaluate the effect of frequency on the maximum magnitude of shear stress created on the embryonic stem cell layer. By applying the fluid-solid interaction method to solve the problem by two-way coupling of the equations, the results show that all the obtained values of shear stress at frequencies of 0.33 and 1 Hz and with frequency difference in cyclic strain (0.33 Hz) and pulsatile flow (1 Hz) are in the suitable range for differentiation of the stem cells to cardiomyocytes. The corresponding shear stress values are 0.00562, 0.02 and 0.01 dyn/cm2, respectively.
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干细胞分化为心肌细胞的机械刺激的有限元分析
心力衰竭是世界上导致死亡的主要原因,其诊断仍有许多缺陷。目前,手术干预治疗心血管疾病仅限于缺乏器官供体移植和免疫抑制治疗的并发症。研究人员正在寻找使受损心脏再生的新方法。组织工程是一项利用具有再生能力的细胞、支架和生长因子的新技术。干细胞具有自我修复和向心肌细胞分化的能力,是心脏组织工程的最佳细胞来源。由于人体内的心肌细胞由于有节奏的心跳而处于循环应变和脉动流的动态环境中,这些机械刺激是干细胞分化、心脏组织功能调节和体内平衡的重要因素。本研究旨在模拟脉冲流和循环应变施加在灌注生物反应器上对用于心脏组织工程的干细胞(心肌细胞)的影响。由于剪切应力激活了转录途径,该参数在干细胞向心肌细胞分化过程中非常有效。本研究试图评估频率对胚胎干细胞层产生的最大剪切应力的影响。应用流固相互作用法对方程进行双向耦合求解,结果表明:得到的剪切应力频率为0.33 Hz和1 Hz,以及循环应变(0.33 Hz)和脉动流量(1 Hz)的频率差值均在干细胞向心肌细胞分化的适宜范围内。相应的剪应力值分别为0.00562、0.02和0.01 dyn/cm2。
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