Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Altındağ, Ankara 06100, Turkey.
Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, Ankara, Turkey.
Biomed Mater. 2021 Aug 17;16(5). doi: 10.1088/1748-605X/ac199a.
In this study, we evaluated cardiomyogenic differentiation of electromechanically stimulated rat bone marrow-derived stem cells (rt-BMSCs) on an acellular bovine pericardium (aBP) and we looked at the functioning of this engineered patch in a rat myocardial infarct (MI) model. aBP was prepared using a detergent-based decellularization procedure followed by rt-BMSCs seeding, and electrical, mechanical, or electromechanical stimulations (3 millisecond pulses of 5 V cmat 1 Hz, 5% stretching) to enhance cardiomyogenic differentiation. Furthermore, the electromechanically stimulated patch was applied to the MI region over 3 weeks. After this period, the retrieved patch and infarct region were evaluated for the presence of calcification, inflammatory reaction (CD68), patch to host tissue cell migration, and structural sarcomere protein expressions. In conjunction with any sign of calcification, a higher number of BrdU-labelled cells, and a low level of CD68 positive cells were observed in the infarct region under electromechanically stimulated conditions compared with static conditions. More importantly, MHC, SAC, Troponin T, and N-cad positive cells were observed in both infarct region, and retrieved engineered patch after 3 weeks. In a clear alignment with other results, our developed acellular patch promoted the expression of cardiomyogenic differentiation factors under electromechanical stimulation. Our engineered patch showed a successful integration with the host tissue followed by the cell migration to the infarct region.
在这项研究中，我们评估了在去细胞牛心包（aBP）上电机械刺激大鼠骨髓源性干细胞（rt-BMSCs）的心肌分化情况，并观察了这种工程化贴片在大鼠心肌梗死（MI）模型中的功能。aBP 是使用基于去污剂的去细胞化程序制备的，然后接种 rt-BMSCs，并进行电、机械或电机械刺激（3 毫秒 5 V cm 的脉冲，1 Hz，5%拉伸）以增强心肌分化。此外，将电机械刺激贴片应用于 MI 区域 3 周。经过这段时间后，对回收的贴片和梗死区域进行钙化、炎症反应（CD68）、贴片与宿主组织细胞迁移以及结构肌节蛋白表达的评估。与任何钙化迹象结合，在电机械刺激条件下与静态条件相比，梗死区域中观察到更多的 BrdU 标记细胞和较少的 CD68 阳性细胞。更重要的是，在 3 周后，在梗死区域和回收的工程化贴片中均观察到 MHC、SAC、肌钙蛋白 T 和 N-cad 阳性细胞。与其他结果一致，我们开发的去细胞贴片在电机械刺激下促进了心肌分化因子的表达。我们的工程化贴片与宿主组织成功整合，随后细胞迁移到梗死区域。
