Stem cell‐based cell therapy for neuroprotection in stroke: A review

Rikhtegar, Reza; Yousefi, Mehdi; Kasmaei, Hosein Delavar; Charsouei, Saeid; Nouri, Mohammad; Shakouri, Seyed Kazem

doi:10.1002/jcb.28207

Cited by 37 publications

(15 citation statements)

References 138 publications

(311 reference statements)

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“…Ischemic stroke is defined as an obstruction of arteries in particular middle cerebral artery, which is responsible for supplying blood to the brain. Immediately after an ischemic stroke attack, decompensated neuronal death and damage occur [147]. Several factors including oxidative stress, apoptosis, edema-mediated by ionic imbalance as well as inflammation are implicated in the pathogenesis of ischemic stroke [148,149,150].…”

Section: Naringenin In Neurodegenerative Diseasesmentioning

confidence: 99%

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective

et al. 2019

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As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge. Besides, appropriate neuroprotective agents are still lacking, which raises the need for new therapeutic agents. In recent years, several reports have introduced naturally-derived compounds as promising alternative treatments for NDs. Among natural entities, flavonoids are multi-target alternatives affecting different pathogenesis mechanisms in neurodegeneration. Naringenin is a natural flavonoid possessing neuroprotective activities. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways for naringenin, which suggest its possible therapeutic applications in several NDs. Here, in this review, the neuroprotective effects of naringenin, as well as its related pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective, are described. Moreover, the need to develop novel naringenin delivery systems is also discussed to solve its widespread pharmacokinetic limitation.

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Section: Naringenin In Neurodegenerative Diseasesmentioning

confidence: 99%

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective

et al. 2019

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“…Second, the contribution from the peripheral immune cells crossing BBB was not addressed in our model and they could also play important roles in the post-ischemic inflammation 93 . Third, since the flow in our chip was bidirectional, generated by a rocking shaker, the endothelial cells would activate different signal pathways of mechanotransduction compared to the unidirectional blood flow in vivo 94,95 .…”

Section: Discussionmentioning

confidence: 99%

Microphysiological stroke model for systematic evaluation of neurorestorative potential of stem cell therapy

Lee

Lyu

Park

et al. 2021

Preprint

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Stem cell therapy is emerging as a promising treatment option to restore a neurological function after ischemic stroke. Despite the growing number of candidate stem cell types, each with unique characteristics, there is a lack of experimental platform to systematically evaluate their neurorestorative potential. When stem cells are transplanted into ischemic brain, the therapeutic efficacy primarily depends on the response of the neurovascular unit (NVU) to these extraneous cells. In this work, we developed an ischemic stroke microphysiological system (MPS) with a functional NVU on a microfluidic chip. Our new chip design facilitated the incorporated cells to form a functional blood-brain barrier (BBB) and restore their in vivo-like behaviors in both healthy and ischemic conditions. We utilized this MPS to track the transplanted stem cells and characterize their neurorestorative behaviors reflected in gene expression levels. Each type of stem cells showed unique neurorestorative effects, primarily through supporting the endogenous recovery, rather than through direct cell replacement. And the recovery of synaptic activities, critical for neurological function, was more tightly correlated with the recovery of the structural and functional integrity in NVU, rather than with the regeneration of neurons itself.

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“…Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have also been examined in preclinical studies [ 112 , 113 , 114 ]. Their pluripotency is an attractive characteristic in relation to its usefulness in treatment.…”

Section: Unsolved Issues Associated With Optimal Treatmentmentioning

confidence: 99%

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Kawabori

Shichinohe

Kuroda

et al. 2020

IJMS

128

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Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.

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Stem cell‐based cell therapy for neuroprotection in stroke: A review

Cited by 37 publications

References 138 publications

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective

Microphysiological stroke model for systematic evaluation of neurorestorative potential of stem cell therapy

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

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