Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

Raed Obaid Saleh, Ali A. Majeed, Ria Margiana, Ola Kamal A. Alkadir,Sami G. Almalki, Pallavi Ghildiyal, Vadim Samusenkov, Noura Kareem Jabber,Yasser Fakri Mustafa, Ahmed Elawady

CELL BIOCHEMISTRY AND FUNCTION(2024)

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摘要
Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naive MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed. Both at the bench and at the bedside, stem cell applications for tissue regeneration and repair are progressing. The therapeutic potential of mesenchymal stem cells (MSCs) isolated from bone marrow and other sources is currently being investigated in stroke patients. Notwithstanding the benefits, MSCs therapy is still constrained by poor survival rates, poor engraftment rates, difficulty homing to the site of damage, and inefficient tissue differentiation. Some of these issues are being investigated by means of genetic engineering of MSCs. The current understanding of the application of genetically modified MSCs in stroke therapy is presented in this review, with a focus on genetic alterations intended to enhance cell survival, homing, angiogenesis, and brain function.
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关键词
cerebral ischemic damage,genetic,mesenchymal stem cell,stroke,treatment
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