The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke

Cunningham, Catriona; Redondo‐Castro, Elena; Allan, Stuart M.

doi:10.1177/0271678x18776802

Cited by 197 publications

(194 citation statements)

References 152 publications

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“…MSCs stimulate endogenous neurogenesis 69,124 Determine specific neurogenic pathway targeted by MSCs Biomarker…”

Section: Biomarker Allogeneic Graftsmentioning

confidence: 99%

“…Accumulating evidence shows that the therapeutic effects of MSCs in different pathologies may be mediated by the paracrine secretion of a broad array of biological active molecules. 61,69 The secretomes and exosomes containing those molecules can be easily isolated from the cells and used as a biodrug. 70,71 In the case of neuroinflammation-related diseases, the intranasal administration of the secretome has been evaluated as a noninvasive and effective route to reach the brain.…”

Section: Bm-mscs Dampen Phagocytic Activity and Stimulate Polarizationmentioning

confidence: 99%

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Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

et al. 2020

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Acquired brain injury (ABI) entails any injury that disrupts neuronal activity and is not degenerative, hereditary, congenital, or induced by birth trauma. Traditional examples of ABI include not only stroke and traumatic brain injury (TBI), but also near drowning, aneurysm, tumor, meningitis and other infections involving the brain, and injuries resulting from lack of oxygen supply to the brain, such as those seen in myocardial infarction. ABI may involve a structural insult, changes to metabolic activity, or disruption to neuronal capabilities.While progressive loss of brain cells and debilitating motor and cognitive deficits play a role in all these disorders, stroke and TBI overlap particularly closely in pathology and impose an immense burden on the American and global populations. AbstractIschemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long-term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM-MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM-MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell-based combination treatments. K E Y W O R D Sbone marrow-derived mesenchymal stem cells, clinical trials, inflammation, ischemic stroke, preclinical studies, traumatic brain injury

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“…MSCs stimulate endogenous neurogenesis 69,124 Determine specific neurogenic pathway targeted by MSCs Biomarker…”

Section: Biomarker Allogeneic Graftsmentioning

confidence: 99%

Section: Bm-mscs Dampen Phagocytic Activity and Stimulate Polarizationmentioning

confidence: 99%

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

et al. 2020

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“…In the ischemic stroke model, the neurogenesis after stroke also depends on T lymphocytes subgroups, different subgroup deficient plays different effect on neurogenesis . Exogenous stem cell therapy confers superior antiinflammatory effects and the robust antiinflammatory action is considered as an important requirement to improve neurogenesis and other regenerative processes after stroke …”

Section: The Role Of Neuroinflammation In Multiple Brain Repair Mechamentioning

confidence: 99%

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

et al. 2018

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Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long-term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post-stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post-stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post-stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

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“…Thus, active MSCs release cytokines, chemokines, growth factors, and microvesicles that act in a feedback loop to control the inflammatory response [10]. The damaged tissue is characterized, in vivo, by the presence of inflammatory cytokines that prime MSCs, acting as a sub-lethal event that can trigger an adaptive response of MSCs to future injury or damage [11]. However, the damaged tissue is also an inhospitable environment that can lead to the premature death of MSCs used for therapy [12] and to an increase in their immunogenicity [13].…”

Section: Introductionmentioning

confidence: 99%

Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells

et al. 2020

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Background: Equine amniotic mesenchymal stromal cells (AMSCs) and their conditioned medium (CM) were evaluated for their ability to inhibit in vitro proliferation of peripheral blood mononuclear cells (PBMCs) with and without priming. Additionally, AMSC immunogenicity was assessed by expression of MHCI and MHCII and their ability to counteract the in vitro inflammatory process. Methods: Horse PBMC proliferation was induced with phytohemagglutinin. AMSC priming was performed with 10 ng/ml of TNF-α, 100 ng/ml of IFN-γ, and a combination of 5 ng/ml of TNF-α and 50 ng/ml of IFN-γ. The CM generated from naïve unprimed and primed AMSCs was also tested to evaluate its effects on equine endometrial cells in an in vitro inflammatory model induced by LPS. Immunogenicity marker expression (MHCI and II) was evaluated by qRT-PCR and by flow cytometry.Results: Priming does not increase MHCI and II expression. Furthermore, the inhibition of PBMC proliferation was comparable between naïve and conditioned cells, with the exception of AMSCs primed with both TNF-α and IFN-γ that had a reduced capacity to inhibit T cell proliferation. However, AMSC viability was lower after priming than under other experimental conditions. CM from naïve and primed AMSCs strongly inhibited PBMC proliferation and counteracted the inflammatory process, rescuing about 65% of endometrial cells treated by LPS.Conclusion: AMSCs and their CM have a strong capacity to inhibit PBMC proliferation, and priming is not necessary to improve their immunosuppressive activity or reactivity in an inflammatory in vitro model.

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The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke

Cited by 197 publications

References 152 publications

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells

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