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.
发表日期:2024
作者:
Yasaman Mehdizadeh Darban, Hamid Askari, Maryam Ghasemi-Kasman, Hanie Yavarpour-Bali, Amirabbas Dehpanah, Parnia Gholizade, Nasrin Nosratiyan
来源:
Current Neuropharmacology
摘要:
中风是一种具有高致残率和死亡率的神经系统疾病。几乎80%的中风病例是缺血性中风,其余的是出血性中风。唯一批准的缺血性中风治疗方法是溶栓和/或血栓切除术。然而,这些治疗方法并不能充分缓解疾病结局,许多患者即使在有效溶栓后仍然残疾。因此,康复治疗对于诱导大脑重塑是必要的。目前,干细胞移植,特别是通过使用诱导多能干细胞(iPSC),被认为是刺激神经发生和大脑重塑的一种有前途的替代疗法。 iPSC 由体细胞通过特定转录因子产生。 iPSC的生物学功能与胚胎干细胞(ESC)相似,包括免疫调节、减少脑血流量、脑水肿和自噬等。尽管 iPSC 疗法在出血性和缺血性中风中都发挥着良好的作用,但其应用存在一定的局限性。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,无细胞疗法作为替代方法可以克服这些限制。本研究回顾了 iPSC 在中风模型中的治疗应用以及这些细胞的潜在机制和限制。此外,还讨论了使用外泌体、凋亡小体和微泡作为替代疗法的无细胞疗法。
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.