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

Abstract Background Mesenchymal stromal cells (MSCs) have significant immunomodulatory and tissue repair capabilities, mediated partly by conditioned media or through secreted extracellular vesicles (MSC-EVs). Infection with SARS-CoV-2 can cause mild to life-threatening illness due to activated immune responses that may be dampened by MSCs or their secretome. Many clinical studies of MSCs have been launched since the beginning of the global pandemic, however, few have been completed and most lack power to assess efficacy. Repeated systematic searches and meta-analyses are needed to understand, in real time, the extent of potential benefit in different patient populations as the evidence emerges. Methods This living systematic review will be maintained to provide up-to-date information as the pandemic evolves. A systematic literature search of Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases will be performed. All clinical studies (e.g., randomized, pseudorandomized and non-randomized controlled trials, uncontrolled trials, and case series) employing MSCs or their secretome as a therapeutic intervention for COVID-19 will be included. Patients must have confirmed SARS-CoV-2 infection. Study screening and data extraction will be performed in duplicate. Information concerning interventions, patient populations, methods of MSC isolation and characterization, primary and secondary clinical and/or laboratory outcomes, and adverse events will be extracted. Key clinical outcomes will be pooled through random-effects meta-analysis to determine the efficacy of MSCs and their secreted products for COVID-19. Discussion Our systematic review and subsequent updates will inform the scientific, medical, and health policy communities as the pandemic evolves to guide decisions on the appropriate use of MSC-related products to treat COVID-19. Systematic review registration PROSPERO CRD 42021225431

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The in vitro effects of platelet products on the biophysiological functions of human bone marrow mesenchymal stromal cells: a systematic review

10.22203/ecm.v041a19 ◽

2021 ◽

Vol 41 ◽

pp. 269-315

Author(s):

J Vun ◽

◽

M Panteli ◽

E Jones ◽

PV Giannoudis

Keyword(s):

Systematic Review ◽

Bone Marrow ◽

Clinical Practice ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Future Research ◽

Signalling Molecules ◽

Combined Use ◽

In Vitro Effects

Platelet products (PP) and bone-marrow aspirate are popular sources of osteoinductive signalling molecules and osteogenic bone marrow mesenchymal stromal cells (BM-MSCs) used in the treatment of impaired bone healing. However, the combined use of PP and BM-MSCs in clinical studies has reported mixed results. Understanding the cellular and molecular interactions between PP and BM-MSCs plays the important role of guiding future research and clinical application. This systematic review investigates the effects of PP on the biophysiological functions of BM-MSCs in in vitro human studies, including (i) proliferation, (ii) migration, (iii) differentiation, (iv) growth factor/cytokine/protein expression, (v) immunomodulation, (vi) chemotactic effect on haematopoietic stem cells, (vii) response to apoptotic stress, and (viii) gene expression. In vitro studies in human have demonstrated the multi-faceted ‘priming effect’ of PP on the biophysiological functions of BM-MSCs. PP has been shown to improve proliferation, migration, osteogenic differentiation, reaction to apoptotic stress as well as immunomodulatory, pro-angiogenic and pro-inflammatory capacities of BM-MSCs. Several factors are highlighted that restrict the transferability of these findings into clinical practice. Therefore, more collaborative in vitro research in humans modelled to reflect clinical practice is required to better understand the effects of PP exposure on the biophysiological function(s) of BM-MSCs in human.

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Systematic review and meta-analysis of preclinical studies testing mesenchymal stromal cells for traumatic brain injury

npj Regenerative Medicine ◽

10.1038/s41536-021-00182-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Francesca Pischiutta ◽

Enrico Caruso ◽

Alessandra Lugo ◽

Helena Cavaleiro ◽

Nino Stocchetti ◽

...

Keyword(s):

Systematic Review ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Mesenchymal Stromal Cells ◽

Effect Size ◽

Stromal Cells ◽

Meta Analysis ◽

Similar Efficacy ◽

Post Injury ◽

Neurological Improvement

AbstractMesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but are hampered by wide variability in treatment responses. We made a systematic review and meta-analysis: (1) to assess the quality of evidence for MSC treatment in TBI rodent models; (2) to determine the effect size of MSCs on sensorimotor function, cognitive function, and anatomical damage; (3) to identify MSC-related and protocol-related variables associated with greater efficacy; (4) to understand whether MSC manipulations boost therapeutic efficacy. The meta-analysis included 80 studies. After TBI, MSCs improved sensorimotor and cognitive deficits and reduced anatomical damage. Stratified meta-analysis on sensorimotor outcome showed similar efficacy for different MSC sources and for syngeneic or xenogenic transplants. Efficacy was greater when MSCs were delivered in the first-week post-injury, and when implanted directly into the lesion cavity. The greatest effect size was for cells embedded in matrices or for MSC-derivatives. MSC therapy is effective in preclinical TBI models, improving sensorimotor, cognitive, and anatomical outcomes, with large effect sizes. These findings support clinical studies in TBI.

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Effectiveness and Safety of Autologous Bone Marrow Stromal Cells Transplantation After Ischemic Stroke: A Meta-Analysis

Medical Science Monitor ◽

10.12659/msm.895081 ◽

2015 ◽

Vol 21 ◽

pp. 2190-2195 ◽

Cited By ~ 9

Author(s):

Pan Li

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Meta Analysis ◽

Autologous Bone Marrow ◽

Marrow Stromal Cells ◽

Autologous Bone

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Mesenchymal stromal cells for COVID-19: A living systematic review protocol

10.1101/2020.04.13.20064162 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gabriel Rada ◽

Javiera Corbalán ◽

Patricio Rojas ◽

Keyword(s):

Systematic Review ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Direct Evidence ◽

Meta Analysis ◽

Grey Literature ◽

Cochrane Central Register ◽

Randomised Trials ◽

Eligibility Criteria ◽

The Impact

ABSTRACTObjectiveTo determine the impact of mesenchymal stromal cells outcomes important to patients with COVID-19.DesignThis is the protocol of a living systematic review.Data sourcesWe will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.Eligibility criteria for selecting studies and methodsWe adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question.We will include randomised trials evaluating the effect of mesenchymal stromal cells versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case we find no direct evidence from randomised trials, or if the direct evidence provides low- or very low-certainty for critical outcomes.Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome.A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates.Ethics and disseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.PROSPERO RegistrationSubmitted to PROSPERO (awaiting ID allocation).

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