The Therapeutic Potential of Mesenchymal Stem Cell–Derived Exosomes in Treatment of Neurodegenerative Diseases

Gorabi, Armita Mahdavi; Kiaie, Nasim; Barreto, George E.; Read, Morgayn I.; Tafti, Hossein Ahmadi; Sahebkar, Amirhossein

doi:10.1007/s12035-019-01663-0

Cited by 101 publications

(67 citation statements)

References 126 publications

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“…MSCs-Exo have been shown to have therapeutic benefits in stroke, TBI, and other neurodegenerative diseases [6,[27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Jia

et al. 2020

Med Sci Monit

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Background: Transplantation of exosomes derived from mesenchymal stem cells (MSCs-Exo) can improve the recovery of neurological function in rats after traumatic brain injury (TBI). We tested a new hypothesis that brain-derived neurotrophic factor (BDNF)-induced MSCs-Exo can effectively promote functional recovery and neurogenesis in rats after TBI. Material/Methods: BM-MSCs of rats were extracted by whole bone marrow culture, BDNF was added to BM-MSCs as an intervention, supernatant was collected, and exosomes were separated and purified by ultracentrifugation. Exosomes were identified by Western blot (WB), transmission electron microscopy (TEM), and particle size analysis and were subsequently used in cell and animal experiments. The experimental animals were divided into a sham group, a PBS group, an MSCs-Exo group, and a BDNF-induced MSCs-Exo group (n=12). An electric cortical contusion impactor (eCCI) was used to cause TBI in all rats except the sham group. We investigated the recovery of sensorimotor function and spatial learning ability, inflammation inhibition, and neuron regeneration in rats after TBI. Results: Compared with the MSCs-Exo group, the BDNF-induced MSCs-Exo group showed better effects in promoting the recovery of sensorimotor function and spatial learning ability. BDNF-induced MSCs-Exo successfully inhibited inflammation and promoted neuronal regeneration in vivo and in vitro. We further analyzed miRNAs in BDNF-induced MSCs-Exo and MSCs-Exo and found that the expression of miR-216a-5p in BDNF-induced MSCs-Exo was significantly higher than that in MSCs-Exo as determined by qRT-PCR. Rescue experiments indicated that miR-216a-5p had a similar function as BDNF-induced MSCs-Exo. Conclusions: We found that BDNF-induced MSCs-Exo can improve cell migration and inhibit apoptosis better than MSCs-Exo in rats after TBI, and the mechanism may be related to the high expression of miR-216a-5p.

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“…MSCs-Exo have been shown to have therapeutic benefits in stroke, TBI, and other neurodegenerative diseases [6,[27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Jia

et al. 2020

Med Sci Monit

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“…8,9 Adult bone marrow-derived stem cells, such as endothelial progenitor cells, hematopoietic, and mesenchymal stem cells (MSCs), have expedited the translation of lab-to-clinic stem cell therapy due to their logistical ease in isolation and amplification, and being relatively free from ethical concerns. 10,11 MSCs have been explored as transplantable donor cells for many experimental models of neurological diseases, 12,13 such as Parkinson's disease, [14][15][16] amyotrophic lateral sclerosis, [17][18][19] Alzheimer's disease, 20,21 and stroke. [22][23][24][25][26][27][28] Cell replacement was initially implicated in MSCs' therapeutic effects, yet with only modest graft survival despite robust functional outcomes, 29 the currently accepted mechanism of action involves bystander repair processes primarily via stem cell-secreted therapeutic factors.…”

Section: Introductionmentioning

confidence: 99%

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy

Kaneko

Lee

Tajiri

et al. 2019

Stem Cells Translational Medicine

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The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration.The optimal dose was 7.5 × 10 6 cells/mL when delivered via the intracarotid artery within 3 days poststroke, although therapeutic effects persisted even when administered at 1 week after stroke. Compared with other mesenchymal stem cells, NCS-01 cells ameliorated both the structural and functional deficits after stroke through a broad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as basic fibroblast growth factor and interleukin-6, but equally importantly we observed for the first time the formation of filopodia by NCS-01 cells under stroke conditions, characterized by cadherin-positive processes extending from the stem cells toward the ischemic cells. Collectively, the present efficacy readouts and the novel filopodiamediated mechanism of action provide solid lab-to-clinic evidence supporting the use of NCS-01 cells for treatment of stroke in the clinical setting.STEM CELLS Transl Med. 2020;9:203-220.wileyonlinelibrary.com/journal/sct3 203 204 KANEKO ET AL.

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“…The intrathecal administration of the MSC/HSC preparation, containing 4 × 10 5 of CD34 + cells into rats that had been subjected to a spinal cord injury, was shown to improve functional outcomes and decrease peripheral concentrations of pro‐inflammatory cytokines (TNF, IL‐1ß, and IL‐6) in the cerebrospinal fluid . Previous studies have reported beneficial effects of stem cell therapy in animal models of ALS; the majority of these studies employed manipulated MCSs, while the use of unmanipulated stem cells and preparations containing HSCs and MSCs has been shown to increase the therapeutic activity of stem cell therapy . Thus, we hypothesized that this treatment might also ameliorate ALS‐like pathology owing to the anti‐inflammatory effects of Neuro‐Cells.…”

Section: Introductionmentioning

confidence: 99%

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

et al. 2019

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Aims:Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 10 6 mesenchymal and hemopoietic human stem cells, containing 5 × 10 5 of CD34 + cells), which showed antiinflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle.Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Celltreated mutants had reduced muscle atrophy and lumbar motor neuron degeneration.This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion:The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. | 505MUNTER ET al.

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The Therapeutic Potential of Mesenchymal Stem Cell–Derived Exosomes in Treatment of Neurodegenerative Diseases

Cited by 101 publications

References 126 publications

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

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