Neural Stem Cells for Early Ischemic Stroke

Hamblin, Milton; Lee, Jean-Pyo

doi:10.3390/ijms22147703

Cited by 28 publications

(12 citation statements)

References 271 publications

(378 reference statements)

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“…In recent years, NSCs have yielded high hopes for the treatment of stroke, especially ischemic cerebrovascular disease [ 6 ]. Theoretically, NSCs transplanted into the penumbra at the edge of cerebral infarction will proliferate for a few generations and then differentiate to supplement neurons and glial cells, thereby repairing damage and improving nerve function.…”

Section: Introductionmentioning

confidence: 99%

Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation

Cai

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cerebral infarct penumbra due to hypoxia and toxin accumulation is not conducive to the transplantation of neural stem cells (NSCs), although mild hypothermia can improve the local microenvironment of the ischemic penumbra and exert neuroprotective effects. However, insufficient understanding of the molecular mechanism by which mild hypothermia protects the brain limits widespread clinical application. This study evaluated the molecular mechanism of mild hypothermia-induced brain protection from the perspective of global protein small ubiquitin-like modifier (SUMO) modification, with the aim of improving NSC transplant survival rates in the penumbra to enhance neurological function. NSCs from neonatal rats were extracted to detect the effects of hypoxia and mild hypothermia on SUMOylation modification levels, cell stemness, and hypoxia-induced injury. Overexpression and knockdown of UBC9 in NSCs were used to evaluate their ability to maintain stemness and withstand hypoxic injury. Finally, a rat middle cerebral artery occlusion (MCAO) model was used to verify the effect of mild hypothermia treatment and UBC9 overexpression on neural function of NSCs following penumbra transplantation in rats. Results showed that hypoxia and mild hypothermia promoted both the SUMOylation modification and maintenance of NSC stemness. Overexpression of UBC9 enhanced the abilities of NSCs to maintain stemness and resist hypoxic injury, while UBC9 knockdown had the opposite effect. Following transplantation into the ischemic penumbra of MCAO model rats, mild hypothermia and Ubc9-overexpressing NSCs significantly reduced cerebral infarct areas and improved neurological function. In conclusion, this study demonstrated that global protein SUMOylation is an important molecular mechanism for NSCs to tolerate hypoxia, and mild hypothermia can further increase the degree of global SUMOylation to enhance the hypoxia tolerance of NSCs, which increases their survival during transplantation in situ and ability to perform nerve repair in the penumbra of cerebral infarction.

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Section: Introductionmentioning

confidence: 99%

Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation

Cai

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The results indicated that the reservation of the cerebral cortex was much better compared to that in the control group only in the group receiving transplantation on day 1 [ 24 ]. Although the origins of stem cells varied, their results indicated that stem cell transplantation in the acute phase of stroke can reduce neurological deficits and improve functional recovery [ 12 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In fact, although some cerebral ischemia patients really survived, they struggled with the impasse of chronic stroke.…”

Section: Discussionmentioning

confidence: 99%

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats

Yeh

Chu

et al. 2022

IJMS

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Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton’s jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats’ cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

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“…In addition, there are abundant sources of NSCs, as NSCs can be directly obtained from neural tissue or generated from the differentiation of embryonic stem cells or induced pluripotent stem cells. Moreover, NSCs have a strong potential for neuronal phenotypic differentiation, chemotaxis, and migration in vivo and in vitro [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Optimal therapeutic conditions for the neural stem cell-based management of ischemic stroke: a systematic review and network meta-analysis based on animal studies

Yang

Qin

et al. 2022

BMC Neurol

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Background In order to promote the clinical translation of preclinical findings, it is imperative to identify the most optimal therapeutic conditions and adopt them for further animal and human studies. This study aimed to fully explore the optimal conditions for neural stem cell (NSC)-based ischemic stroke treatment based on animal studies. Methods The PubMed, Ovid-Embase, and Web of Science databases were searched in December 2021. The screening of search results, extraction of relevant data, and evaluation of study quality were performed independently by two reviewers. Results In total, 52 studies were included for data analysis. Traditional meta-analysis showed that NSCs significantly reduced the modified neurological severity score (mNSS) and volume of cerebral infarct in animal models of ischemic stroke. Network meta-analysis showed that allogeneic embryonic tissue was the best source of NSCs. Further, intracerebral transplantation was the most optimal route of NSC transplantation, and the acute phase was the most suitable stage for intervention. The optimal number of NSCs for transplantation was 1–5×105 in mouse models and 1×106 or 1.8×106 in rat models. Conclusions We systematically explored the therapeutic strategy of NSCs in ischemic stroke, but additional research is required to develop optimal therapeutic strategies based on NSCs. Moreover, it is necessary to further improve and standardize the design, implementation, measuring standards, and reporting of animal-based studies to promote the development of better animal experiments and clinical research.

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Neural Stem Cells for Early Ischemic Stroke

Cited by 28 publications

References 271 publications

Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation

Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats

Optimal therapeutic conditions for the neural stem cell-based management of ischemic stroke: a systematic review and network meta-analysis based on animal studies

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