Mesenchymal stem cells: therapeutic outlook for stroke

Honmou, Osamu; Onodera, Rie; Sasaki, Masanori; Waxman, Stephen G.; Kocsis, Jeffery D.

doi:10.1016/j.molmed.2012.02.003

Cited by 158 publications

(115 citation statements)

References 50 publications

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“…Behavioral gains associated with administration of MSCs days to weeks poststroke might reflect many different restorative or immunologic processes. 4,7,8,11 Together, these results emphasize that translational MSC studies need to carefully consider optimal time windows for various therapeutic targets. This issue is of particular importance to consideration of autologous MSC therapies.…”

Section: Resultsmentioning

confidence: 86%

“…6 Preclinical studies suggest that MSCs do not replace lost neurons after stroke but instead provide benefit through multiple parallel processes that modulate the tissue microenvironment, including paracrine delivery of growth factors, local and distant immunomodulation, reduced apoptosis, reduced perilesional glial scar formation, promotion of axonal outgrowth and synaptic remodeling, astrocytic and oligodendrocyte precursor cell proliferation, neurogenesis, and angiogenesis. 4,[7][8][9][10][11] This is a potential advantage over pharmacologic therapies that act via a single treatment mechanism. 7,8,11 In addition, MSCs have an excellent safety record in clinical trials of humans with many different diseases.…”

mentioning

confidence: 99%

“…4,[7][8][9][10][11] This is a potential advantage over pharmacologic therapies that act via a single treatment mechanism. 7,8,11 In addition, MSCs have an excellent safety record in clinical trials of humans with many different diseases. [12][13][14] The purpose of the current study was to review preclinical studies examining MSC therapy after ischemic stroke.…”

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confidence: 99%

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Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

et al. 2014

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Objectives:To evaluate the quality of preclinical evidence for mesenchymal stromal cell (MSC) treatment of ischemic stroke, determine effect size of MSC therapy, and identify clinical measures that correlate with differences in MSC effects.Methods: A literature search identified studies of MSCs in animal models of cerebral ischemia. For each, a Quality Score was derived, and effect size of MSCs was determined for the most common behavioral and histologic endpoints.Results: Of 46 studies, 44 reported that MSCs significantly improved outcome. The median Quality Score was 5.5 (of 10). The median effect size was 1.78 for modified Neurological Severity Score, 1.73 for the adhesive removal test, 1.02 for the rotarod test, and 0.93 for infarct volume reduction. Quality Score correlated significantly and positively with effect size for the modified Neurological Severity Score. Effect sizes varied significantly with clinical measures such as administration route (intracerebral . intra-arterial . IV, although effect size for IV was nonetheless very large at 1.55) and species receiving MSCs (primate . rat . mouse). Because many MSC mechanisms are restorative, analyses were repeated examining only the 36 preclinical studies administering MSCs $24 hours poststroke; results were overall very similar. Conclusions:In preclinical studies, MSCs have consistently improved multiple outcome measures, with very large effect sizes. Results were robust across species studied, administration route, species of MSC origin, timing, degree of immunogenicity, and dose, and in the presence of comorbidities. In contrast to meta-analyses of preclinical data for other stroke therapies, higher-quality MSC preclinical studies were associated with larger behavioral gains. These findings support the utility of further studies to translate MSCs in the treatment of ischemic stroke in humans.

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Section: Resultsmentioning

confidence: 86%

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confidence: 99%

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Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

et al. 2014

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“…Recently, BMSCs have been used in clinical trials to treat stroke patients (23,35). The protocol has been tested in nonhuman primates and human patients who receive intravenous injections of their own BMSCs (34,40,46).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Bone Marrow Mesenchymal Stem Cells Improved Neurovascular Regeneration and Rescued Neuropsychiatric Deficits after Neonatal Stroke in Rats

Wei

Ferdinand

et al. 2015

Cell Transplant

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Neonatal stroke is a major cause of mortality and long-term morbidity in infants and children. Currently, very limited therapeutic strategies are available to protect the developing brain against ischemic damage and promote brain repairs for pediatric patients. Moreover, children who experienced neonatal stroke often have developmental social behavior problems. Cellular therapy using bone marrow mesenchymal stem cells (BMSCs) has emerged as a regenerative therapy after stroke. In the present investigation, neonatal stroke of postnatal day 7 (P7) rat pups was treated with noninvasive and brain-specific intranasal delivery of BMSCs at 6 h and 3 days after stroke (1 × 10 6 cells/animal). Prior to transplantation, BMSCs were subjected to hypoxic preconditioning to enhance their tolerance and regenerative properties. The effects on regenerative activities and stroke-induced sensorimotor and social behavioral deficits were specifically examined at P24 of juvenile age. The BMSC treatment significantly reduced infarct size and blood-brain barrier disruption, promoted angiogenesis, neurogenesis, neurovascular repair, and improved local cerebral blood flow in the ischemic cortex. BMSC-treated rats showed better sensorimotor and olfactory functional recovery than saline-treated animals, measured by the adhesive removal test and buried food finding test. In social behavioral tests, we observed functional and social behavioral deficits in P24 rats subjected to stroke at P7, while the BMSC treatment significantly improved the performance of stroke animals. Overall, intranasal BMSC transplantation after neonatal stroke shows neuroprotection and great potential as a regenerative therapy to enhance neurovascular regeneration and improve functional recovery observed at the juvenile stage of development.

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“…MSCs have been shown to exert profound immunomodulatory properties and have gained approval as a treatment in certain countries for graft versus host disease. Several meta-analyses have consistently demonstrated their treatment effects in various animal models of stroke [19][20][21][22][23][24]. In fact, MSCs are likely the most widely studied type of cell therapy in the preclinical stroke literature [1][2][3].…”

Section: Bone Marrow Stromal Cellsmentioning

confidence: 99%

Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies Enhance Stroke Recovery?

Satani

Savitz

2016

Neurotherapeutics

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Inflammation within the brain and in peripheral tissues contributes to brain injury following ischemic stroke. Therapeutic modulation of the inflammatory response has been actively pursued as a novel stroke treatment approach for decades, without success. In recent years, extensive studies support the high potential for cell-based therapies to become a new treatment modality for stroke and other neurological disorders. In this review, we explore different types of cellular therapies and discuss how they modulate central and peripheral inflammatory processes after stroke. Apart from identifying potential targets for cell therapy, we also discuss paracrine and immunomodulatory mechanisms of cell therapy.

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Mesenchymal stem cells: therapeutic outlook for stroke

Cited by 158 publications

References 50 publications

Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

Intranasal Delivery of Bone Marrow Mesenchymal Stem Cells Improved Neurovascular Regeneration and Rescued Neuropsychiatric Deficits after Neonatal Stroke in Rats

Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies Enhance Stroke Recovery?

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