Stem cell therapy displays significant effects of functional improvement for ischemic stroke, offering hope for the preservation of neural tissue in the acute phase of stroke and the replacement of lost tissue in the chronic stage ( Wei et al., 2017). Over the past decades, stem cell-based therapy has attracted great interest as an emerging treatment in stroke in the hope that it can repair the damaged central neural networks ( Wan Safwani et al., 2017 Choi et al., 2018). Limited numbers of stroke patients can benefit from these approaches and achieve good outcomes ( Detante et al., 2017). However, this technique is not yet fully developed, and the efficacy and safety of endovascular reperfusion beyond 6 h remains controversial ( Berkhemer et al., 2015 Smith, 2019). Mechanical thrombectomy exhibits the significant therapeutic efficacy in acute ischemic stroke caused by intracranial proximal artery occlusion. Fewer than 5% of ischemic stroke patients receive such treatment and still suffer post-treatment neurological deficits with no therapy available to promote recovery ( Lyden et al., 2019). However, thrombolysis has a narrow therapeutic window, being clinically effective only within 4.5 h after stroke and losing its effect when the thrombus is large or the stroke is extensive ( Bhaskar et al., 2018). Currently, there are no proven options for stroke patients aside from dissolution of thrombus via tissue plasminogen activator (e.g., alteplase), or mechanical thrombectomy ( Hacke et al., 2008 Powers et al., 2015 Saver et al., 2016). Rapid restoration of cerebral blood flow is the focus of the treatment for acute stroke. The necrotic portion, also known as the ischemic core, is surrounded by the peri-infarct region or penumbra that represents the functionally impaired but potentially salvageable tissue and is the primary target for the developing neuroprotective strategies ( Candelario-Jalil and Paul, 2021). This produces carbon monoxide with consequent irreversible necrosis of brain cells ( Rastogi et al., 2006). As a result of cerebral ischemia, excitatory amino acids react with tissues and generate a large number of calcium ions and free radicals. Ischemic stroke is caused by occlusion of a supply artery due to embolus or thrombus. Approximately 15 million individuals worldwide are affected by stroke each year, of whom 5 million will ultimately die and 5 million will suffer long-term disability ( Roy-O’Reilly and McCullough, 2014). With an increasing elderly population, the mortality and morbidity of stroke are increasing. It is classified as hemorrhagic (13%), caused by rupture of blood vessels, or ischemic (87%), caused by disruption of blood supply ( Kalladka and Muir, 2014). Stroke, one of the major diseases of the central nervous system, is a global health problem with limited treatment options. In this review, we focus on the following issues: the scientific data from preclinical studies and clinical trials of MSCs in the treatment of stroke the potential mechanisms underlying MSC-based therapy for stroke the challenges related to the timing and delivery of MSCs and MSC senescence. Although MSCs have shown promising results in the treatment of stroke, there remain many challenges to overcome prior to their therapeutic application. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as a novel strategy for various diseases including stroke due to their unique properties that include easy isolation, multipotent differentiation potential and strong paracrine capacity. Despite advances in pharmacological and surgical therapy, treatment for functional rehabilitation following stroke is limited with a consequent serious impact on quality of life. Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is the leading cause of morbidity and mortality worldwide.
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