Kokaia Zaal, Darsalia Vladimer
Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.
Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden.
Results Probl Cell Differ. 2018;66:249-263. doi: 10.1007/978-3-319-93485-3_11.
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. It takes place when the brain does not receive sufficient blood supply due to the blood clot in the vessels or narrowing of vessels' inner space due to accumulation of fat products. Apart from thrombolysis (dissolving of blood clot) and thrombectomy (surgical removal of blood clot or widening of vessel inner area) during the first hours after an ischemic stroke, no effective treatment to improve functional recovery exists in the post-ischemic phase. Due to their narrow therapeutic time window, thrombolysis and thrombectomy are unavailable to more than 80% of stroke patients.Many experimental studies carried out in animal models of stroke have demonstrated that stem cell transplantation may become a new therapeutic strategy in stroke. Transplantation of stem cells of different origin and stage of development has been shown to lead to improvement in experimental models of stroke through several mechanisms including neuronal replacement, modulation of cellular and synaptic plasticity and inflammation, neuroprotection and stimulation of angiogenesis. Several clinical studies and trials based on stem cell delivery in stroke patients are in progress with goal of improvements of functional recovery through mechanisms other than neuronal replacement. These approaches may provide therapeutic benefit, but generation of specific neurons for reconstruction of stroke-injured neural circuitry remains ultimate challenge. For this purpose, neural stem cells could be developed from multiple sources and fated to adopt required neuronal phenotype.
缺血性中风是全球第二大常见死因,也是导致残疾的主要原因。当大脑由于血管中的血凝块或由于脂肪产物积累导致血管内部空间变窄而无法获得足够的血液供应时,就会发生缺血性中风。除了在缺血性中风后的最初几个小时内进行溶栓(溶解血凝块)和血栓切除术(手术清除血凝块或扩大血管内部区域)外,在缺血后阶段不存在改善功能恢复的有效治疗方法。由于治疗时间窗狭窄,超过80%的中风患者无法进行溶栓和血栓切除术。
在中风动物模型中进行的许多实验研究表明,干细胞移植可能成为中风的一种新治疗策略。不同来源和发育阶段的干细胞移植已被证明可通过多种机制改善中风实验模型,这些机制包括神经元替代、细胞和突触可塑性及炎症调节、神经保护和血管生成刺激。目前正在进行几项基于向中风患者递送干细胞的临床研究和试验,目标是通过神经元替代以外的机制改善功能恢复。这些方法可能会带来治疗益处,但生成特定神经元以重建中风损伤的神经回路仍然是最终挑战。为此,可以从多个来源开发神经干细胞,并使其定向分化为所需的神经元表型。