Mesenchymal Stem Cell Therapy in Ischemic Stroke: A Meta‐analysis of Preclinical Studies

Sarmah, Deepaneeta; Agrawal, Vishal; Rane, Pallavi; Bhute, Shashikala; Watanabe, Manabu; Kalia, Kiran; Ghosh, Zhumur; Dave, Kunjan R.; Yavagal, Dileep R.; Bhattacharya, Pallab

doi:10.1002/cpt.927

Cited by 49 publications

(44 citation statements)

References 77 publications

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“…23 A recent meta-analysis of preclinical studies of MSCs in ischemic stroke showed that MSCs were infused either immediately or over a period varying from 24 hours to 4 weeks; none of the 64 publications used an 8-week post-MCAO MSC administration time. 25 In our stroke model, we obtained T2-weighted images 8 weeks after MCAO and excluded rats with infarcted volumes smaller than 230 mm 3 . H & E staining of brain sections from animals killed at 8 weeks after MCAO induction also indicated a chronic stage of cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction

Namioka

Sasaki

et al. 2019

Journal of Neurosurgery

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OBJECTIVEIntravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of cerebral infarction. Although clinical studies are ongoing, most studies have focused on the acute or subacute phase of stroke. In the present study, MSCs derived from bone marrow of rats were intravenously infused 8 weeks after the induction of a middle cerebral artery occlusion (MCAO) to investigate whether delayed systemic injection of MSCs improves functional outcome in the chronic phase of stroke in rats.METHODSEight weeks after induction of the MCAO, the rats were randomized and intravenously infused with either MSCs or vehicle. Ischemic volume and behavioral performance were examined. Blood-brain barrier (BBB) integrity was assessed by quantifying the leakage of Evans blue into the brain parenchyma after intravenous infusion. Immunohistochemical analysis was also performed to evaluate the stability of the BBB.RESULTSMotor recovery was better in the MSC-treated group than in the vehicle-treated group, with rapid improvement (evident at 1 week post-infusion). In MSC-treated rats, reduced BBB leakage and increased microvasculature/repair and neovascularization were observed.CONCLUSIONSThese results indicate that the systemic infusion of MSCs results in functional improvement, which is associated with structural changes in the chronic phase of cerebral infarction, including in the stabilization of the BBB.

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Section: Discussionmentioning

confidence: 99%

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction

Namioka

Sasaki

et al. 2019

Journal of Neurosurgery

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“…The therapeutic potential of MSCs is associated with their ability to moderate the regenerative niche in a wound site, which commonly involves an ischemic environment (Bhang et al, 2011;Chen et al, 2016;Sarmah et al, 2018). This study observed that both bMSCs and ASCs showed significantly increased survival following 3D aggregation in the ischemic environment, while the opposite effect was seen in FB.…”

Section: Isr Helps Manage Environmental Stressors and Extends Stem mentioning

confidence: 83%

Aggregation‐induced integrated stress response rejuvenates culture‐expanded human mesenchymal stem cells

Bijonowski

Yuan

et al. 2020

Biotech & Bioengineering

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Protein homeostasis is critical for cellular function, as loss of homeostasis is attributed to aging and the accumulation of unwanted proteins. Human mesenchymal stem cells (MSCs) have shown promising therapeutic potential due to their impressive abilities to secrete inflammatory modulators, angiogenic, and regenerative cytokines. However, there exists the problem of human MSC expansion with compromised therapeutic quality. Duringin vitro expansion, human MSCs are plated on stiff plastics and undergo culture adaptation, which results in aberrant proliferation, shifts in metabolism, and decreased autophagic activity. It has previously been shown that three‐dimensional (3D) aggregation can reverse some of these alterations by heightening autophagy and recovering the metabolic state back to a naïve phenotype. To further understand the proteostasis in human MSC culture, this study investigated the effects of 3D aggregation on the human MSC proteome to determine the specific pathways altered by aggregation. The 3D aggregates and 2D cultures of human MSCs derived from bone marrow (bMSC) and adipose tissue (ASC) were analyzed along with differentiated human dermal fibroblasts (FB). The proteomics analysis showed the elevated eukaryotic initiation factor 2 pathway and the upregulated activity of the integrated stress response (ISR) in 3D aggregates. Specific protein quantification further determined that bMSC and ASC responded to ISR, while FB did not. 3D aggregation significantly increased the ischemic survival of bMSCs and ASCs. Perturbation of ISR with small molecules salubrinal and GSK2606414 resulted in differential responses of bMSC, ASC, and FB. This study indicates that aggregation‐based preconditioning culture holds the potential for improving the therapeutic efficacy of expanded human MSCs via the establishment of ISR and homeostasis.

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“…Терапевтические эффекты МСК были широко исследованы в экспериментальных работах [33,34,[36][37][38] на животных моделях ишемии головного мозга. Было показано, что трансплантация МСК уменьшает моторный дефицит и улучшает выполнение поведенческих тестов.…”

Section: нскunclassified

Cell therapy for ischemic stroke. Stem cell types and results of pre-clinical trials

Namestnikova¹,

Таирова²,

Sukhinich³

et al. 2018

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Ишемический инсульт (ИИ)-одна из ведущих причин смертности и инвалидизации во всем мире. На сегодняшний день основным методом лечения этого заболевания является ранняя реперфузионная терапия, которая ограничена узким терапевтическим окном, составляющим 4,5 ч для внутривенного тромболизиса [1] и 6 ч для эндоваскулярных методик [2]. Однако даже при своевременном применении этих технологий с последующим использованием антиагрегантов, антикоагулянтов и ранней нейрореабилитации у большинства пациентов сохраняется пожизнен ный неврологический дефицит в связи с формиро ванием зоны инфаркта мозга. Эффективных методов лечения ИИ в позднем восстановительном периоде не существует. Также не существует ни одного нейропротективного препарата, эффективность которого была бы достоверно подтверждена в многоцентровых рандомизированных клинических

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Mesenchymal Stem Cell Therapy in Ischemic Stroke: A Meta‐analysis of Preclinical Studies

Cited by 49 publications

References 77 publications

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction

Aggregation‐induced integrated stress response rejuvenates culture‐expanded human mesenchymal stem cells

Cell therapy for ischemic stroke. Stem cell types and results of pre-clinical trials

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