MGM Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
Research, Innovation and Development (R,I&D), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
Hum Cell. 2022 Nov;35(6):1633-1639. doi: 10.1007/s13577-022-00785-3. Epub 2022 Sep 6.
Endothelial dysfunction is one of the key cornerstone complications of emerging and re-emerging viruses which lead to vascular leakage and a high mortality rate. The mechanism that regulates the origin of endothelial dysregulation is not completely elucidated. Currently, there are no potential pharmacological treatments and curable management for such diseases. In this sense, mesenchymal stromal/stem cells (MSCs) has been emerging to be a promising therapeutic strategy in restoring endothelial barrier function in various lung disease, including ALI and ARDS. The mechanism of the role of MSCs in restoring endothelial integrity among single-strand RNA (ssRNA) viruses that target endothelial cells remains elusive. Thus, we have discussed the therapeutic role of MSCs in restoring vascular integrity by (i) inhibiting the metalloprotease activity thereby preventing the cleavage of tight junction proteins, which are essential for maintaining membrane integrity (ii) possessing antioxidant properties which neutralize the excessive ROS production due to virus infection and its associated hyper host immune response (iii) modulating micro RNAs that regulate the endothelial activation and its integrity by downregulating the inflammatory response during ssRNA infection.
内皮功能障碍是新兴和再现病毒导致血管渗漏和高死亡率的关键基石并发症之一。调节内皮失调起源的机制尚未完全阐明。目前,针对此类疾病尚无潜在的药理学治疗和可治愈的管理方法。在这种情况下,间充质基质/干细胞(MSCs)作为一种有前途的治疗策略,正在各种肺部疾病(包括ALI 和 ARDS)中恢复内皮屏障功能。MSCs 在恢复针对内皮细胞的单链 RNA(ssRNA)病毒的内皮完整性方面的作用机制仍不清楚。因此,我们讨论了 MSCs 通过以下方式恢复血管完整性的治疗作用:(i)抑制金属蛋白酶活性,从而防止紧密连接蛋白的裂解,而紧密连接蛋白对于维持膜完整性至关重要;(ii)具有抗氧化特性,可中和由于病毒感染及其相关的过度宿主免疫反应引起的过多 ROS 产生;(iii)通过下调 ssRNA 感染期间的炎症反应,调节调节内皮激活及其完整性的 microRNAs。