Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India.
Stempeutics Research Pvt. Ltd., 3rd Floor, Manipal Hospitals Whitefield #143, EPIP Industrial Area, ITPL Main Road, Bangalore, 560 048, India.
Stem Cell Rev Rep. 2024 Nov;20(8):2138-2154. doi: 10.1007/s12015-024-10787-3. Epub 2024 Sep 21.
Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed.
缺血性疾病的特征是血液流向相应器官受阻,其中心脏和大脑的缺血是最突出的表现,具有共同的病理生理机制和危险因素。虽然大多数血管再通治疗旨在恢复血液流动,但由于治疗方法的治疗窗口有限,这可能具有挑战性。很长一段时间以来,间充质基质细胞一直被用于治疗脑和心脏缺血。然而,它们的应用受到以下因素的限制:输送效率低下或在植入缺血微环境后细胞存活率低。尽管如此,目前仍有多项研究侧重于使用过表达治疗基因的工程间充质基质细胞作为基于细胞的基因治疗来恢复血管生成。本综述深入探讨了间充质基质细胞在血管生成中的应用,以及工程间充质基质细胞在心脏和大脑缺血治疗中的应用。此外,还讨论了与间充质基质细胞遗传修饰相关的安全问题。