Neural stem cell transplantation therapy for brain ischemic stroke: Review and perspectives

Abstract

Brain ischemic stroke is one of the most common causes of death and disability, currently has no efficient therapeutic strategy in clinic. Due to irreversible functional neurons loss and neural tissue injury, stem cell transplantation may be the most promising treatment approach. Neural stem cells (NSCs) as the special type of stem cells only exist in the nervous system, can differentiate into neurons, astrocytes, and oligodendrocytes, and have the abilities to compensate insufficient endogenous nerve cells and improve the inflammatory microenvironment of cell survival. In this review, we focused on the important role of NSCs therapy for brain ischemic stroke, mainly introduced the methods of optimizing the therapeutic efficacy of NSC transplantation, such as transfection and overexpression of specific genes, pretreatment of NSCs with inflammatory factors, and co-transplantation with cytokines. Next, we discussed the potential problems of NSC transplantation which seriously limited their rapid clinical transformation and application. Finally, we expected a new research topic in the field of stem cell research. Based on the bystander effect, exosomes derived from NSCs can overcome many of the risks and difficulties associated with cell therapy. Thus, as natural seed resource of nervous system, NSCs-based cell-free treatment is a newly therapy strategy, will play more important role in treating ischemic stroke in the future.

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

“…Ischemic stroke is one of the three most prevalent causes of death and disability that disproportionally targets the rapidly increasing aged population (Zhang et al, 2019). Similar to other neurodegenerative diseases, the hope of NSC transplants as a therapeutic option in ischemic stroke is twofold: (i) to repopulate the lesion site through cell differentiation and neurogenesis, and tissue repair; and (ii) to modulate the pro-inflammatory microenvironment.…”

Recent Advances in Cell-Based Therapies for Ischemic Stroke

“…NSCs in the SVZ mainly migrate along the rostral migratory stream to the olfactory bulb, whereas NSCs in the SGZ migrate to the granule cell layer where they finally differentiate into various neural cells and integrate into neuronal networks [84]. In addition, the human brain may contain another stem cell pool in the deep ventral region of the prefrontal cortex due to the highly developed prefrontal lobe [85].…”

“…Although transplanted NSCs are expected to differentiate into various neural cells rather than other stem cells, it remains unclear to what extent this contributes to functional recovery. The current understanding is that transplanted NSCs likely prevent neuronal apoptosis, exert immunomodulatory effects inside and outside the brain, increase endogenous neuronal regeneration and angiogenesis, and inhibit glial scar formation mainly via paracrine and autocrine secretion of various neurotrophic factors rather than differentiation [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 109 , 110 ] ( Table 2 ).…”

Propofol Attenuates Inflammatory Damage <i>via</i> Inhibiting NLRP1-Casp1-Casp6 Signaling in Ischemic Brain Injury

“…Stroke is a disease caused by cerebral vascular obstruction and/or rupture which induces brain damage and leads to permanent disability and death. 1,2) The ischemic stroke is 80-85% of total stroke. 3) Various risk factors are involved in the pathogenesis for the neurons of ischemic stroke, including inflammation, oxidative stress and excitotoxicity.…”