Abstract
Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs), mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s) by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.
Highlights
The number of stroke-related deaths is increasing and stroke remains one of the major causes of deaths and disability worldwide [1, 2]
Several alternative approaches including the use of embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs) have been tried in hopes of improving the drastic neuronal and functional impairment that usually follows a stroke insult
The outcomes of various preclinical studies have been encouraging, with engrafted stem cells succeeding in bringing about neurofunctional improvements
Summary
The number of stroke-related deaths is increasing and stroke remains one of the major causes of deaths and disability worldwide [1, 2]. Based on the initial number of cells engrafted and the route of administration, the necessary first step in restoring damaged cellular elements following stroke is the migration of transplanted cells to damaged brain regions This is usually achieved through the ability of engrafted stem/progenitors cells to target damaged regions [63] in response to different chemotactic signals of specific cytokines, such as the vascular cell adhesion molecule 1, stromal-derived factor 1, monocyte chemotactic protein-1, chemokine (C–C motif) ligand 2 [21]. The study suggests that a higher dose of BM-MNC (3 × 106 or more) provided a better outcome in stroke patients [66] In another recent clinical trial, improved neurological function with no tumor formation or adverse events was demonstrated following engraftment of an immortalized human neural stem-cell line [67]. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small single-arm phase 1 trials of intracerebrally implanted cells [76]
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