A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke

Reis, Cesar; Wilkinson, Michael; Reis, Haley; Akyol, Onat; Gospodarev, Vadim; Araujo, Camila; Chen, Sheng; Zhang, Junyi

doi:10.1155/2017/3267352

Cited by 27 publications

(25 citation statements)

References 74 publications

(82 reference statements)

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“…Stem cell therapy is currently one of the most promising strategies for the treatment of various neurodegenerative diseases [ 1 , 2 , 3 , 4 ]. Recent research showed that mesenchymal stem cell (MSC) therapy could be an effective therapeutic option for global cerebral ischemia [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Pretreatment with the NADPH Oxidase Inhibitor Apocynin on the Therapeutic Efficacy of Human Placenta-Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage

Min

Kim

Bae

et al. 2018

IJMS

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Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on intracerebral hemorrhage (ICH). Enhancement of the therapeutic efficacy of MSCs in ICH is necessary, considering the diseases high association with mortality and morbidity. Various preconditioning methods to enhance the beneficial properties of MSCs have been introduced. We suggested apocynin, a well-known nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, as a novel preconditioning regimen to enhance the therapeutic efficacy of MSCs in ICH. Rat ICH models were made using bacterial collagenase. 24 h after ICH induction, the rats were randomly divided into apocynin-preconditioned MSC-treated (Apo-MSC), naïve MSC-treated and control groups. Hematoma volume, brain edema, and degenerating neuron count were compared at 48 h after the ICH induction. The expression of tight junction proteins (occludin, zona occludens [ZO]-1) were also compared. Hematoma size, hemispheric enlargement and degenerating neuron count were significantly lower in the Apo-MSC group than in the naïve MSC group (p = 0.004, 0.013 and 0.043, respectively), while the expression of occludin was higher (p = 0.024). Apocynin treatment enhances the therapeutic efficacy of MSCs in ICH in the acute stage, through the improvement of the beneficial properties of MSCs, such as neuroprotection and the reinforcement of endovascular integrity of cerebral vasculature.

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Section: Introductionmentioning

confidence: 99%

Effect of Pretreatment with the NADPH Oxidase Inhibitor Apocynin on the Therapeutic Efficacy of Human Placenta-Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage

Min

Kim

Bae

et al. 2018

IJMS

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“… 1 Ischemia results in reduced neuron number and interrupted neural axon network, and formation of a defected environment around the ischemic region, which prohibits brain self-healing, eventually resulting in the permanent loss of nerve tissue or disabled brain function. 1 , 4 , 5 Over 50,000,000 people are suffering from IS of various degrees in the world. 6 The annual mortality rate is close to 10%, and nearly 50% of stroke survivors are left with disabling sequelae.…”

Section: Introductionmentioning

confidence: 99%

“… 6 The annual mortality rate is close to 10%, and nearly 50% of stroke survivors are left with disabling sequelae. 1 , 2 , 4 Poststroke rehabilitation therapy is scant, and currently the most efficient medicine for IS in clinical settings is tissue plasminogen activator. 1 , 7 However, it functions mainly at the early stage of ischemia with a short time window, which may increase the risk of cerebral hemorrhage, and therefore, its clinical application is severely limited.…”

Section: Introductionmentioning

confidence: 99%

“…Mesenchymal stem cells (MSCs) are derived from mesoderm and have the capacity of regeneration and differentiation. MSCs can differentiate into various lineages such as NSCs, which can further differentiate into neurons, astrocytes, oligodendrocytes and so on, 4 , 15 , 16 with low immunogenicity and high histocompatibility. 1 , 15 Compared with other types of stem cells, such as NSCs, EPCs and HSCs, MSCs are more accessible as they can be easily obtained from umbilical cord, bone marrow, fat and other tissues, and can proliferate rapidly in vitro with little ethical constraints.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cell transplantation as an effective treatment strategy for ischemic stroke in Asia: a meta-analysis of controlled trials

Xue

Wang

Yan

2018

TCRM

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ObjectiveThe aim of this study was to evaluate the efficacy and safety of the mesenchymal stem cell (MSC) therapy in patients with ischemic stroke (IS).Materials and methodsClinical trials involved in this research were searched from PubMed, Web of Science, Cochrane Library, Embase, Wanfang and CNKI database. Therapeutic effects of MSC therapy were assessed according to National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI), Fugl-Meyer Assessment (FMA) and Functional Independence Measure (FIM), and its safety was evaluated based on adverse events.ResultsThis research covered 23 trials including 1,279 IS patients. Based on our analysis, the overall condition of IS patients significantly improved after MSC therapy, indicated by decreased NIHSS and increased BI, FMA and FIM scores. Our analysis also showed that the treatment effects in the MSC transplantation group were superior to those in the control group (routine medication therapy) with statistical significance for NIHSS (1 month after therapy: odds ratio [OR]=−1.92, CI=−3.49 to −0.34, P=0.02; 3 months after therapy: OR=−2.65, CI=−3.40 to −1.90, P<0.00001), BI (1 month after therapy: OR=0.99, CI=0.19–1.79, P=0.02; 6 months after therapy: OR=10.10, CI=3.07–17.14, P=0.005), FMA (3 months after therapy: OR=10.20, CI=3.70–16.70, P=0.002; 6 months after therapy: OR=10.82, CI=6.45–15.18, P<0.00001) and FIM (1 month after therapy: OR=15.61, CI=−0.02 to 31.24, P=0.05; 6 months after therapy: OR=16.56, CI=9.06–24.06, P<0.0001). No serious adverse events were reported during MSC therapy.ConclusionMSC therapy is safe and effective in treating IS by improving the neurological deficits, motor function and daily life quality of patients.

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“…be further harmed by the excessive production of reactive oxygen species (ROS) due to the restoration of oxygen and nutrients to damaged brain cells, causing a so-called ischemia-reperfusion (I/R) injury [3,[6][7][8][9]. Major contributors to the pathological process of ischemic stroke include the overproduction of ROS, dramatically increased extracellular glutamate levels, and the potent activation of neuroin ammation responses [6,7,9].…”

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confidence: 99%

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

Xie¹,

Zeng²,

Xu³

et al. 2020

Preprint

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Background: Ischemic stroke results in high morbidity and mortality, and mitochondrial dysfunctions play a crucial role in the associated pathological process. Although exogenous mitochondria were used to treat ischemic stroke-induced brain injury, its effects and related mechanisms remain poorly understood, as is the fate of exogenous mitochondria during/after internalization by targeted cells. Methods: The mitochondrial morphology, membrane potential, DNA copy number, mitochondrial stress, metabolic characteristics and tumorigenicity of mNSCs and Neuro-2a cells were evaluated. Hypoxia/reoxygenation-induced cell injury was performed, and after mitochondrial supplementation, the viability, ROS levels, apoptosis and transcriptomic changes were assessed by CCK-8, DCHF-DA probes, flow cytometry, WB and next-generation sequencing analyses. The fate of exogenous mitochondria was further explored using fluorescent dyes and fusion protein analyses during/after internalization by targeted cells. Rat tMCAO models were generated using a suture-occluded method, and at 24 h after mitochondrial transplantation, behavioral changes and brain infarction areas were estimated by multiple score scales and TTC staining, respectively. Results: In this research, we found that mitochondria of Neuro-2a cells had some notable differences compared to that of mNSCs on mitochondrial membrane potential, DNA copy number, stress response and metabolic characteristics, but their shapes were similar and were both no tumorigenicity. Exogenous mitochondrial treatment could increase the cellular viability in an oxygen-dependent pattern, decrease the cellular ROS generation and apoptosis, and alter the transcriptomic characteristics after subjected to hypoxia/reoxygenation in vitro. Selective component recombination might occur during/after internalization of exogenous mitochondria by host cells and was observed with mitochondrial fluorescent dyes and engineered fusion protein. Moreover, mitochondrial transplantation could significantly improve tMCAO-induced rat neurobehavioral deficiency and brain infarction. Conclusions: The results of our present study offer a promising therapeutic strategy for ischemia/reperfusion-induced brain injury and provide preliminary insights regarding the effects and fate of exogenous mitochondria during/after being internalized into host cells.

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A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke

Cited by 27 publications

References 74 publications

Effect of Pretreatment with the NADPH Oxidase Inhibitor Apocynin on the Therapeutic Efficacy of Human Placenta-Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage

Effect of Pretreatment with the NADPH Oxidase Inhibitor Apocynin on the Therapeutic Efficacy of Human Placenta-Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage

Mesenchymal stem cell transplantation as an effective treatment strategy for ischemic stroke in Asia: a meta-analysis of controlled trials

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

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