MicroRNAs in vascular tissue engineering and post-ischemic neovascularization.
MicroRNAs in vascular tissue engineering and post-ischemic neovascularization.
复制标题
DOI：
10.1016/j.addr.2015.05.003
复制
发表时间：
2015-07-01
影响因子：
16.1
通讯作者：
Emanueli C
中科院分区：
文献类型：
--
作者：
Caputo M;Saif J;Rajakaruna C;Brooks M;Angelini GD;Emanueli C
越来越多的患有先天性心脏病的儿科患者存活至成年，尽管仍有持续的临床需求。因此，仍然有革命性的新策略来纠正血管解剖缺陷的空间。成年患者在缺血性血管疾病的不良后果下存活的时间也更长，特别是在斑块侵蚀和破裂引起的急性冠状动脉综合征之后。血管组织工程和治疗性血管生成为这些患者提供了新的希望。这两种方法在实验室研究中都显示出了希望，但尚未能够提供临床成功的明确证据。有必要对生物材料、分子医学以及细胞和分子疗法进行更多的研究。这篇综述文章的重点是通过靶向microRNA提供的新机会，用于血管组织工程中的血管细胞的生产和更大的授权，或通过放大常驻微血管网络增加缺血组织的血液灌注。miR在血管组织工程中的应用示意图。可以收集来自患者的细胞，扩增并进行miR调节策略以产生所需规格的细胞。可以调节多能干细胞以抑制自我更新并促进向所需祖细胞分化。此外，祖细胞的miR调节可以允许细胞维持在祖细胞状态或向特定后代分化，从而促进模块化细胞治疗策略。经修饰的细胞可以被加载到支架上用于植入，或者可以用于在植入患者之前在体外产生完整的组织和器官。MiR修饰策略也可以直接用于缺血组织中以调节血管生成。可以从干细胞或祖细胞中分离携带miR的“所需”货物的细胞外囊泡（EV），用于直接注射到缺血组织中。
Increasing numbers of paediatric patients with congenital heart defects are surviving to adulthood, albeit with continuing clinical needs. Hence, there is still scope for revolutionary new strategies to correct vascular anatomical defects. Adult patients are also surviving longer with the adverse consequences of ischemic vascular disease, especially after acute coronary syndromes brought on by plaque erosion and rupture. Vascular tissue engineering and therapeutic angiogenesis provide new hope for these patients. Both approaches have shown promise in laboratory studies, but have not yet been able to deliver clear evidence of clinical success. More research into biomaterials, molecular medicine and cell and molecular therapies is necessary. This review article focuses on the new opportunities offered by targeting microRNAs for the improved production and greater empowerment of vascular cells for use in vascular tissue engineering or for increasing blood perfusion of ischemic tissues by amplifying the resident microvascular network. Schematic of application of miRs in vascular tissue engineering. Cells from patient could be collected, expanded and be subjected to miR modulation strategies to generate cells of desired specification. Pluripotent stem cells can be modulated to inhibit self-renewal and promote differentiation toward a desired progenitor cell. Also miR modulation of the progenitor cells may permit maintenance of the cells in a progenitor state or differentiation toward specific progeny thereby facilitating a modular cell therapy strategy. The modified cells can be loaded onto scaffolds for implantation or can be used to generate intact tissues and organs in vitro before implantation in the patient. MiR modification strategies can also be used directly in ischemic tissues to regulate angiogenesis. Extracellular vesicles (EVs) carrying the ‘desired’ cargo of miR can be isolated from stem or progenitor cells for direct injection into ischemic tissue.