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工程化间充质基质细胞在心脏和脑缺血中增强血管生成的治疗应用。

Therapeutic Applications of Engineered Mesenchymal Stromal Cells for Enhanced Angiogenesis in Cardiac and Cerebral Ischemia.

机构信息

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.

出版信息

Stem Cell Rev Rep. 2024 Nov;20(8):2138-2154. doi: 10.1007/s12015-024-10787-3. Epub 2024 Sep 21.

DOI:10.1007/s12015-024-10787-3
PMID:39305405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11554727/
Abstract

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.

摘要

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。

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本文引用的文献

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The issue of heterogeneity of MSC-based advanced therapy medicinal products-a review.基于间充质干细胞的先进治疗药品的异质性问题——综述
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Extracellular Microvesicles vs. Mitochondria: Competing for the Top Spot in Cardiovascular Regenerative Medicine.细胞外囊泡与线粒体:在心血管再生医学中争夺榜首。
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线粒体转移通过线粒体自噬介导内皮细胞植入。
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Understanding the Angiogenic Characteristics of Clinical-Grade Mesenchymal Stromal Cells Isolated from Human Umbilical Cord.了解从人脐带中分离出的临床级间充质基质细胞的血管生成特性。
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Highly efficient genome editing via CRISPR-Cas9 ribonucleoprotein (RNP) delivery in mesenchymal stem cells.通过 CRISPR-Cas9 核糖核蛋白 (RNP) 递送来实现间充质干细胞中的高效基因组编辑。
BMB Rep. 2024 Jan;57(1):60-65. doi: 10.5483/BMBRep.2023-0113.
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Hybrid spheroids containing mesenchymal stem cells promote therapeutic angiogenesis by increasing engraftment of co-transplanted endothelial colony-forming cells in vivo.含间充质干细胞的杂交球体通过增加体内共移植的内皮祖细胞的植入来促进治疗性血管生成。
Stem Cell Res Ther. 2023 Aug 2;14(1):193. doi: 10.1186/s13287-023-03435-z.
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Novel Gene-Modified Mesenchymal Stem Cell Therapy Reverses Impaired Wound Healing in Ischemic Limbs.新型基因修饰间充质干细胞疗法可逆转缺血肢体的创面愈合受损。
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CSF2RB overexpression promotes the protective effects of mesenchymal stromal cells against ischemic heart injury.CSF2RB 过表达促进间充质基质细胞对缺血性心脏损伤的保护作用。
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Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments.过表达脑源性神经营养因子的工程化间充质干细胞可保护大脑免受创伤性脑损伤诱导的神经元死亡、神经功能缺损和认知障碍。
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