World-Wide Efficacy of Bone Marrow Derived Mesenchymal Stromal Cells in Preclinical Ischemic Stroke Models: Systematic Review and Meta-Analysis

Satani, Nikunj; Cai, Chunyan; Giridhar, Kaavya; McGhiey, Daryl; George, Sarah; Parsha, Kaushik; Nghiem, Duyen M.; Valenzuela, Krystal S; Riecke, Jenny; Vahidy, Farhaan S; Savitz, Sean I

doi:10.3389/fneur.2019.00405

Cited by 35 publications

(49 citation statements)

References 34 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is a substantial body of evidence showing that mesenchymal stem cells (MSCs) improve functional outcomes in rodent models of cerebral ischaemia, as previously reviewed by Satani and colleagues [3]. In phase I/II clinical trials, MSCs have been suggested to be a safe and feasible therapy for ischaemic stroke [4,5].…”

Section: Introductionmentioning

confidence: 99%

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

et al. 2020

View full text Add to dashboard Cite

Background: Mesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles-collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia. Methods: Stroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection. Results: IL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a~30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke. Conclusions: Our results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.

show abstract

Section: Introductionmentioning

confidence: 99%

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

et al. 2020

View full text Add to dashboard Cite

show abstract

“…One promising candidate for stroke therapy is mesenchymal stem cells (MSC). A recent systematic review and meta-analysis of 141 studies demonstrated that bone marrow-derived MSC transplantation leads to improvements in functional outcomes in preclinical models of cerebral ischaemia 4. Initially it was thought that MSCs promote repair and ameliorate functional deficits by differentiating into parenchymal cells 5.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysisTherapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysis

et al. 2020

View full text Add to dashboard Cite

ObjectivesCurrently there is a paucity of clinically available regenerative therapies for stroke. Extracellular vesicles (EV) have been investigated for their potential as modulators of regeneration in the poststroke brain. This systematic review and meta-analysis aims to provide a summary of the efficacy of therapeutic EVs in preclinical stroke models, to inform future research in this emerging field.MethodsStudies were identified by a comprehensive literature search of two online sources and subsequent screening. Studies using lesion volume or neurological score as outcome measures were included. Standardised mean difference (SMD) and 95% CIs were calculated using a restricted maximum likelihood random effects model. Publication bias was assessed with Egger’s regression and presented as funnel plots with trim and fill analysis. Subgroup analysis was performed to assess the effects of different study variables. Study quality and risk of bias were assessed using the CAMARADES checklist.ResultsA total of 20 publications were included in the systematic review, of which 19 were assessed in the meta-analysis (43 comparisons). Overall, EV interventions improved lesion volume (SMD: −1.95, 95% CI −2.72 to 1.18) and neurological scores (SMD: −1.26, 95% CI −1.64 to 0.87) compared with control groups. Funnel plots were asymmetrical suggesting publication bias, and trim and fill analysis predicted seven missing studies for lesion volume. Subgroup analysis suggested administration at 0–23 hours after stroke was the most effective timepoint for EV treatment. The median score on the CAMARADES checklist was 7 (IQR: 5–8).ConclusionsEVs may offer a promising new avenue for stroke therapies, as EV-based interventions had positive impacts on lesion volume and neurological score in preclinical stroke models.PROSPERO registration numberCRD42019134925.

show abstract

“…103 BM-MSCs administration between 2 and 7 days of injury significantly increased health benefits compared to 12 to 24 hours and >7 days. 119 Delivery at 7 days post-stroke has been most commonly reported in the literature, which may be related to the specific brain environment at that time, with decreased glutamate and brain edema. 120 After stroke, the brain microenvironment is constantly changing, with increased excitotoxicity, inflammatory reaction, and trophic factor expressions.…”

Section: Optimal Dose Timing and Age Of Stem Cellsmentioning

confidence: 99%

Optimizing Stem Cell Therapy after Ischemic Brain Injury

et al. 2020

View full text Add to dashboard Cite

Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and <i>in vivo</i> potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.

show abstract

World-Wide Efficacy of Bone Marrow Derived Mesenchymal Stromal Cells in Preclinical Ischemic Stroke Models: Systematic Review and Meta-Analysis

Cited by 35 publications

References 34 publications

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Therapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysisTherapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysis

Optimizing Stem Cell Therapy after Ischemic Brain Injury

Contact Info

Product

Resources

About