Intravenous Infusion of Mesenchymal Stem Cells Enhances Therapeutic Efficacy of Reperfusion Therapy in Cerebral Ischemia

Kiyose, Ryo; Sasaki, Masanori; Kataoka‐Sasaki, Yuko; Nakazaki, Masahito; Nagahama, Hiroshi; Magota, Hirotoshi; Oka, Shinichi; Ukai, Ryo; Takemura, Mitsuhiro; Yokoyama, Takahiro; Kocsis, Jeffery D.

doi:10.1016/j.wneu.2021.02.056

Cited by 11 publications

(14 citation statements)

References 32 publications

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“…Our findings revealed that transplanting MSC 24 h after ischemia improved the functional (motor) impairment in adult rats significantly. Other studies have found that in locus transplanted MSC improves functional outcomes after 7 days following a stroke [44,45].…”

Section: Discussionmentioning

confidence: 93%

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Nucci

Oliveira

Ferreira

et al. 2022

Cells

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The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2–G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit.

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Section: Discussionmentioning

confidence: 93%

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Nucci

Oliveira

Ferreira

et al. 2022

Cells

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“…We previously reported on the safety, feasibility, and potential therapeutic efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with cerebral infarction [ 27 ] and subacute SCI [ 28 ]. The intravenous infusion of MSCs derived from bone marrow improves functional outcomes in experimental animal models of stroke [ 4 - 7 , 9 - 11 ], SCI [ 13 , 14 , 16 , 24 , 30 , 31 ], neonatal hypoxic ischemia [ 12 ], chronic epilepsy [ 17 ], cerebral small vessel disease [ 8 , 32 ], amyotrophic lateral sclerosis [ 33 , 34 ], and peripheral nerve injury [ 18 , 21 ]. Although the mechanisms underlying these beneficial effects have not been fully elucidated, potential mechanisms include neuroprotection and immunomodulation [ 14 ], the induction of axonal sprouting [ 13 ], remyelination [ 13 ], the restoration of the blood-brain and blood–spinal cord barriers [ 13 , 24 ], and the enhancement of remote gene expression responses [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

et al. 2022

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Background Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury. Objective The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury. Methods The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion. Results We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan. Conclusions Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury. Trial Registration Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc International Registered Report Identifier (IRRID) DERR1-10.2196/37898

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“…Is there a connection between BMSC therapy and better infarction volume and gut microbiota regulation? A magnetic resonance imaging (MRI) assessment of the ischemic lesion volume is necessary to provide an answer to this query[ 6 ]. Some researchers have used MRI measures for ischemic lesion volume in their research after BMSC injection in MCAO model rats, according to the literature[ 7 , 8 ].…”

Section: To the Editormentioning

confidence: 99%

“…Some researchers have used MRI measures for ischemic lesion volume in their research after BMSC injection in MCAO model rats, according to the literature[ 7 , 8 ]. Immunohistochemistry, enzyme-linked immunosorbent test, and numerous other behavioral function tests, in addition to MRI measures[ 6 , 9 - 12 ], are strongly advised in study of Zhao et al [ 1 ]. However, to determine whether there is a connection between stroke recovery and gut microbiota regulation following treatment with bone marrow-derived mesenchymal stem cells, the results of previous studies (such as assessment of neuronal nuclei (NeuN) and VEGF expression and measurement of rat endothelial cell antigen 1 and platelet-derived growth factor receptors (PDGF-R), treadmill stress test and MRI studies, and measurement of infarct volume) could be compared to the results of Zhao et al [ 1 ].…”

Section: To the Editormentioning

confidence: 99%

Bone marrow mesenchymal stem cell treatment improves post-stroke cerebral function recovery by regulating gut microbiota in rats

Sheykhhasan¹,

Poondla²

2022

WJSC

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Intravenous Infusion of Mesenchymal Stem Cells Enhances Therapeutic Efficacy of Reperfusion Therapy in Cerebral Ischemia

Cited by 11 publications

References 32 publications

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

Bone marrow mesenchymal stem cell treatment improves post-stroke cerebral function recovery by regulating gut microbiota in rats

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