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诱导多能干细胞在中风治疗中的作用。

The Role of Induced Pluripotent Stem Cells in the Treatment of Stroke.

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

出版信息

Curr Neuropharmacol. 2024;22(14):2368-2383. doi: 10.2174/1570159X22666240603084558.

DOI:10.2174/1570159X22666240603084558
PMID:39403058
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11451314/
Abstract

Stroke is a neurological disorder with high disability and mortality rates. Almost 80% of stroke cases are ischemic stroke, and the remaining are hemorrhagic stroke. The only approved treatment for ischemic stroke is thrombolysis and/or thrombectomy. However, these treatments cannot sufficiently relieve the disease outcome, and many patients remain disabled even after effective thrombolysis. Therefore, rehabilitative therapies are necessary to induce remodeling in the brain. Currently, stem cell transplantation, especially via the use of induced pluripotent stem cells (iPSCs), is considered a promising alternative therapy for stimulating neurogenesis and brain remodeling. iPSCs are generated from somatic cells by specific transcription factors. The biological functions of iPSCs are similar to those of embryonic stem cells (ESCs), including immunomodulation, reduced cerebral blood flow, cerebral edema, and autophagy. Although iPSC therapy plays a promising role in both hemorrhagic and ischemic stroke, its application is associated with certain limitations. Tumor formation, immune rejection, stem cell survival, and migration are some concerns associated with stem cell therapy. Therefore, cell-free therapy as an alternative method can overcome these limitations. This study reviews the therapeutic application of iPSCs in stroke models and the underlying mechanisms and constraints of these cells. Moreover, cell-free therapy using exosomes, apoptotic bodies, and microvesicles as alternative treatments is discussed.

摘要

中风是一种具有高残疾率和死亡率的神经紊乱疾病。近 80%的中风病例为缺血性中风,其余为出血性中风。缺血性中风唯一被批准的治疗方法是溶栓和/或血栓切除术。然而,这些治疗方法并不能充分缓解疾病的预后,许多患者即使经过有效的溶栓治疗仍然残疾。因此,康复疗法对于诱导大脑重塑是必要的。目前,干细胞移植,特别是使用诱导多能干细胞(iPSCs),被认为是一种有前途的替代疗法,可以刺激神经发生和大脑重塑。iPSCs 是通过特定的转录因子从体细胞中产生的。iPSCs 的生物学功能与胚胎干细胞(ESCs)相似,包括免疫调节、减少脑血流量、脑水肿和自噬。尽管 iPSC 治疗在出血性和缺血性中风中都有很大的作用,但它的应用也存在一些局限性。肿瘤形成、免疫排斥、干细胞存活和迁移是与干细胞治疗相关的一些问题。因此,无细胞治疗作为一种替代方法可以克服这些局限性。本研究综述了 iPSCs 在中风模型中的治疗应用及其潜在机制和限制。此外,还讨论了使用外泌体、凋亡小体和微囊泡作为替代治疗的无细胞治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11451314/ac630ccf9b3a/CN-22-2368_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11451314/a3a677fd1c91/CN-22-2368_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11451314/ac630ccf9b3a/CN-22-2368_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11451314/a3a677fd1c91/CN-22-2368_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11451314/ac630ccf9b3a/CN-22-2368_F2.jpg

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Adv Sci (Weinh). 2023 Nov;10(33):e2302527. doi: 10.1002/advs.202302527. Epub 2023 Oct 22.
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Neuroprotection of Stem Cells Against Ischemic Brain Injury: From Bench to Clinic.干细胞对缺血性脑损伤的神经保护作用:从基础到临床。
Transl Stroke Res. 2024 Aug;15(4):691-713. doi: 10.1007/s12975-023-01163-3. Epub 2023 Jul 7.
3
First-in-human clinical trial of transplantation of iPSC-derived NS/PCs in subacute complete spinal cord injury: Study protocol.
纳米技术在缺血性中风中的作用:靶向治疗与诊断的进展以改善临床结局
J Funct Biomater. 2025 Jan 1;16(1):8. doi: 10.3390/jfb16010008.
人诱导多能干细胞衍生的神经干细胞/祖细胞移植治疗亚急性完全性脊髓损伤的首次人体临床试验:研究方案。
Regen Ther. 2021 Sep 7;18:321-333. doi: 10.1016/j.reth.2021.08.005. eCollection 2021 Dec.
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Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents.患者来源的神经胶质丰富祖细胞修复由于啮齿动物的白质中风和血管性痴呆导致的功能缺陷。
Sci Transl Med. 2021 Apr 21;13(590). doi: 10.1126/scitranslmed.aaz6747.
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Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model.神经松弛素底物缓激肽、神经降压素和 P 物质增强人脑微血管通透性的体外模型。
J Neuroendocrinol. 2021 Feb;33(2):e12931. doi: 10.1111/jne.12931. Epub 2021 Jan 28.
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Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs.使用人诱导多能干细胞衍生的神经前体细胞和少突胶质前体细胞治疗Canavan病的细胞疗法。
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