Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys

AbstractCortical injury, such as injuries after stroke or age-related ischemic events, triggers a cascade of degeneration accompanied by inflammatory responses that mediate neurological deficits. Therapeutics that modulate such neuroinflammatory responses in the aging brain have the potential to reduce neurological dysfunction and promote recovery. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are lipid-bound, nanoscale vesicles that can modulate inflammation and enhance recovery in rodent stroke models. We recently assessed the efficacy of intravenous infusions of MSC-EVs (24-h and 14-days post-injury) as a treatment in aged rhesus monkeys (Macaca mulatta) with cortical injury that induced impairment of fine motor function of the hand. Aged monkeys treated with EVs after injury recovered motor function more rapidly and more fully than aged monkeys given a vehicle control. Here, we describe EV-mediated inflammatory changes using histological assays to quantify differences in markers of neuroinflammation in brain tissue between EV and vehicle-treated aged monkeys. The activation status of microglia, the innate macrophages of the brain, is critical to cell fate after injury. Our findings demonstrate that EV treatment after injury is associated with greater densities of ramified, homeostatic microglia, along with reduced pro-inflammatory microglial markers. These findings are consistent with a phenotypic switch of inflammatory hypertrophic microglia towards ant...
Source: AGE - Category: Geriatrics Source Type: research

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Authors: Olaru DG, Olaru A, Kassem GH, Popescu-Drigă MV, Pinoşanu LR, Dumitraşcu DI, Popescu EL, Hermann DM, Popa-Wagner A Abstract Stroke has limited restorative treatment options. In search of new therapeutic strategies for the ischemic brain, cell-based therapies offered new hope, which has been, in the meanwhile, converted into a more realistic approach recognizing difficulties related to unfavorable environments causing low survival rates of transplanted neuronal precursors. Stem cell therapies are based on the transplantation of neuronal precursor cells (NPCs), adult stem cells propagated in cell culture o...
Source: Romanian Journal of Morphology and Embryology - Category: General Medicine Tags: Rom J Morphol Embryol Source Type: research
Abstract Stroke is a serious, life-threatening condition demanding vigorous search for new therapies. Recent research has focused on stem cell-based therapies as a viable choice following ischemic stroke, based on studies displaying that stem cells transplanted to the brain not only survive, but also cause functional recovery. Growth factors defined as polypeptides that regulate the growth and differentiation of many cell types. Many studies have demonstrated that combination use of growth factors may increase results by stimulation of endogenous neurogenesis, anti-inflammatory, neuroprotection properties, and enh...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
Abstract Due to the limitation in treatment window of the rtPA (recombinant tissue plasminogen activator), the development of delayed treatment for stroke is needed. We previously reported that there is a difference in neurogenesis and neuroblast migration patterns in different mouse stroke models (proximal and distal middle cerebral artery occlusion models, pMCAo or dMCAo). Specifically, compared to robust neurogenesis and substantial migration of newly born neuroblasts in pMCAo model, dMCAo only illicit limited neurogenesis and migration of neuroblasts towards ischemic area. One potential reason for this differe...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
AbstractStroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55  days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volum...
Source: Translational Stroke Research - Category: Neurology Source Type: research
CONCLUSIONS In a rat model of CIRI following MCAO, EA activated the NOTCH pathway, promoted the expression of miR-223, increased the number of NSCs, and reduced the expression of PTEN. PMID: 31883264 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Conclusion: MSCs are still the preferred cells for cell replacement in stroke therapy, while RMNE6 cells need to be modified.
Source: Neurology India - Category: Neurology Authors: Source Type: research
Pius PadayattiNeurology India 2019 67(6):1491-1491
Source: Neurology India - Category: Neurology Authors: Source Type: research
Source: Clinical Interventions in Aging - Category: Geriatrics Tags: Clinical Interventions in Aging Source Type: research
CONCLUSIONS: Highly arbourised neurons are more sensitive to ischaemic injury than NPs which did however develop marked vulnerability to prolonged injury with reoxygenation. These observations imply that therapeutic potential may be highly dependent of the developmental state of the neurons we aim to protect. PMID: 31837459 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research
This study offers a preliminary evidence of the role of IA MSCs in regulating inflammasome by modulating ASIC1a.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
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