Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil.
National Center for Structural Biology and Bioimaging - CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil.
Cells. 2020 Jul 7;9(7):1629. doi: 10.3390/cells9071629.
Chagas disease discovered more than a century ago remains an incurable disease. The objective of this work was to investigate the therapeutic potential of cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a model of chronic Chagasic cardiomyopathy (CCC). Mouse embryonic stem cells (mESC) were characterized, transduced with luciferase, and submitted to cardiac differentiation. CM-mESC were labeled with superparamagnetic iron oxide particles. To induce CCC, mice were infected with Brazil strain trypomastigotes. At 150 days post-infection (dpi), infected animals were treated with CM-mESC or PBS. Cells were detected by magnetic resonance imaging (MRI) and bioluminescence. Cardiac function was evaluated by MRI and electrocardiogram at 150 and 196 dpi. CCC mice showed significant differences in MRI and ECG parameters compared to non-infected mice. However, no differences were observed in contractile and electrical parameters between cell and PBS injected groups, 45 days after cell transplantation. Cells were detected 24 h after transplantation by MRI. CM-mESC bioluminescence tracking demonstrated over 90% decrease in signal 8 days after treatment. Nevertheless, the Infected + CM-mESC group showed a significant reduction in the percentage of collagen fibers when compared to the Infected + PBS group. In conclusion, CM-mESC therapy was not effective in reversing cardiac functional changes induced by Chagas disease despite some improvement in myocardial fibrosis.
一个多世纪前发现的恰加斯病仍然是一种无法治愈的疾病。本工作的目的是研究来源于小鼠胚胎干细胞（CM-mESC）的心肌细胞在慢性恰加斯心肌病（CCC）模型中的治疗潜力。对小鼠胚胎干细胞（mESC）进行了特征描述、转染了荧光素酶，并进行了心脏分化。CM-mESC 被超顺磁性氧化铁颗粒标记。为了诱导 CCC，用巴西株锥虫感染小鼠。在感染后 150 天（dpi），用 CM-mESC 或 PBS 处理感染动物。通过磁共振成像（MRI）和生物发光检测细胞。在 150 和 196 dpi 通过 MRI 和心电图评估心脏功能。与未感染的小鼠相比，CCC 小鼠在 MRI 和 ECG 参数上显示出显著差异。然而，在细胞移植后 45 天，在收缩和电参数方面，细胞和 PBS 注射组之间没有差异。移植后 24 小时通过 MRI 检测到细胞。CM-mESC 生物发光示踪显示，治疗 8 天后信号降低了 90%以上。然而，与感染+ PBS 组相比，感染+CM-mESC 组的胶原纤维百分比显著降低。总之，尽管心肌纤维化有一定改善，但 CM-mESC 治疗并不能有效逆转恰加斯病引起的心脏功能变化。
