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

Bonsack, Brooke; Corey, Sydney; Shear, Alex; Heyck, Matt; Cozene, Blaise; Sadanandan, Nadia; Zhang, Henry; Gonzales-Portillo, Bella; Sheyner, Michael; Borlongan, Cesar V.

doi:10.1111/cns.13378

Cited by 53 publications

(46 citation statements)

References 118 publications

(214 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Traumatic brain injury (TBI) is one of the most common cause of disability and mortality worldwide both in children and adolescents and may have a strong correlation with neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease [ 1 , 2 ]. TBI is an acquired brain injury (ABI), not hereditary neither congenital or induced by a birth trauma which may be recognized as mild, moderate or severe following the application of the Glasgow coma scale (GCS) [ 3 , 4 ]. The parameters evaluated in the GCS are motor performance, verbal responses and eye opening: the obtained total score may indicate a severe (3–8), moderate (9–12) or mild TBI (13–15).…”

Section: Traumatic Brain Injury (Tbi)mentioning

confidence: 99%

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

Irrera

Russo

Pallio

et al. 2020

IJMS

View full text Add to dashboard Cite

Traumatic brain injury (TBI) represents an important problem of global health. The damage related to TBI is first due to the direct injury and then to a secondary phase in which neuroinflammation plays a key role. NLRP3 inflammasome is a component of the innate immune response and different diseases, such as neurodegenerative diseases, are characterized by NLRP3 activation. This review aims to describe NLRP3 inflammasome and the consequences related to its activation following TBI. NLRP3, caspase-1, IL-1β, and IL-18 are significantly upregulated after TBI, therefore, the use of nonspecific, but mostly specific NLRP3 inhibitors is useful to ameliorate the damage post-TBI characterized by neuroinflammation. Moreover, NLRP3 and the molecules associated with its activation may be considered as biomarkers and predictive factors for other neurodegenerative diseases consequent to TBI. Complications such as continuous stimuli or viral infections, such as the SARS-CoV-2 infection, may worsen the prognosis of TBI, altering the immune response and increasing the neuroinflammatory processes related to NLRP3, whose activation occurs both in TBI and in SARS-CoV-2 infection. This review points out the role of NLRP3 in TBI and highlights the hypothesis that NLRP3 may be considered as a potential therapeutic target for the management of neuroinflammation in TBI.

show abstract

Section: Traumatic Brain Injury (Tbi)mentioning

confidence: 99%

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

Irrera

Russo

Pallio

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The research group of Ibarra reveals that immunization with neural derived peptides possesses neurogenic and regenerative properties which render motor and sensitive recovery in the chronic stage of SCI 10 . Such combined targeting of neurogenesis and regeneration may be similarly applied to TBI, since the pathology of TBI manifests with impaired stem cell potencies, as recognized in the cell therapy campaign noted in the other papers described here 5‐7 …”

mentioning

confidence: 92%

“…Next, our laboratory further elucidates the potential benefits, as well as caveats associated with cell therapy for TBI 6 . This review paper tackles neuroinflammation as a major cell death mechanism that closely approximates the secondary cell death in TBI.…”

mentioning

confidence: 99%

“…The articles in this special issue probe the pathology of CNS trauma, including TBI and SIC, and begin to understand potential therapeutic modalities. Along this line, the proposed cell therapy 5‐7 and drug and immunization treatments 8‐10 offer new directions in the management of TBI. These promising therapies warrant serious consideration as we translate them into clinical applications.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Traumatic brain injury

Bailes

Borlongan

2020

CNS Neurosci Ther

Self Cite

View full text Add to dashboard Cite

Traumatic brain injury (TBI) stands as a major cause of mortality and morbidity around the world. More than 30% of injury-related deaths in the United States involve TBI. 1,2 TBI entails two phases of injury, namely an initial head trauma via an external force that results in mechanical damage to brain tissue and a secondary biochemical cascades including inflammation, apoptosis, oxidative stress, and other pathophysiological complications that propel further brain degeneration. 3,4 Treatment options for TBI remain limited, indicating an urgent need to examine novel therapeutic modalities designed to protect or to regenerate the injured brain.This special issue compiles recent advances in TBI research focused on cell-based regenerative medicine and pharmacologic therapies. We envision that rigorous translational research will provide the necessary testbed for ushering safe and effective therapeutics from the laboratory to the clinic.Yasuhara and colleagues 5 review the field of cell therapy for TBI and a relevant brain disorder, stroke. Here, they identify technical challenges that accompany cell transplantation, such as cell dose, timing, and delivery. In particular, they outline important preclinical investigations that are warranted to translate induced pluripotent stem cells for clinical applications in TBI and stroke.Next, our laboratory further elucidates the potential benefits, as well as caveats associated with cell therapy for TBI. 6 This review paper tackles neuroinflammation as a major cell death mechanism that closely approximates the secondary cell death in TBI. We also recognize that because neuroinflammation ensues immediately after TBI onset but also persists over time, it presents a large therapeutic window for cell therapy intervention. We provide encouraging laboratory studies detailing the success of cell transplantation in mitigating the inflammation-plagued secondary cell death of TBI.Recognizing that cell therapy may not be a magic bullet, Willing and co-workers 7 offer a combination therapy. Here, they show the potential of combining cell therapy with drugs that target signaling pathways of the neuro-immune-inflammatory axis. The concept posits that since singular targeting of a cell death pathway mostly fails, drugs that engage multiple pathways will likely promote improved sequestration of degenerative processes for TBI.The next two papers indeed advance novel drugs that encompass multiple targeting of cell death pathways. The paper by Dore and teammates demonstrate the potential of engaging the lipid metabolite prostaglandin E2 (PGE 2 ) as therapeutic targets to treat repetitive concussions and other acute brain injuries. 8 PGE 2 binding with the EP2 receptor activates adenylate cyclase and phosphorylates various cellular targets can lead to multiple neuroprotective processes, including anti-inflammation. In a similar fashion, Greig and co-investigators 9 reveal that the small molecular weight drug (-)-phenserine tartrate (PhenT), originally developed for Alzheimer's disease, effectivel...

show abstract

“…Mesenchymal stem cell (MSC) transplantation has been demonstrated to improve functional and pathological recovery in cerebral ischemia [6]. In the condition of cerebral ischemia, the MSC transplantation engenders the migration of endogenous neuronal progenitor cells and alleviates the neuroinflammation associated with acquired brain injury [7,8]. Of note, administration of adipose tissue-derived MSCs (ASCs) leads to functional recovery of cerebral lesions and reduces apoptosis, yet promotes neurogenesis and proliferation [9].…”

Section: Introductionmentioning

confidence: 99%

Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis

Zhang

Liu

et al. 2021

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Cerebral ischemia-reperfusion (I/R) injury, the most common form of stroke, has high mortality and often brings persistent and serious brain dysfunction among survivors. Administration of adipose-derived mesenchymal stem cells (ASCs) has been suggested to alleviate the I/R brain injury, but the mechanism remains uncharacterized. Here, we aimed at investigating the mechanism of ASCs and their extracellular vesicles (EVs) in the repair of or protection from I/R injury. Methods We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/RP) neuron model. ASCs or ASC-derived EVs (ASC-EVs) were co-cultured with neurons. RT-qPCR and Western blot analyses determined microRNA (miRNA)-22-3p, BMP2, BMF, and KDM6B expression in neurons upon treatment with ASC-EVs. Bioinformatics analysis predicted the binding between miR-22-3p and KDM6B. Using gain- and loss-of-function methods, we tested the impact of these molecules on I/R injury in vivo and in vitro. Results Treatment with ASCs and ASC-derived EVs significantly alleviated the I/R brain injury in vivo, elevated neuron viability in vitro, and decreased apoptosis. Interestingly, miR-22-3p was upregulated in ASC-EVs, and treatment with EV-miR-22-3p inhibitor led to increased apoptosis and decreased neuronal. Of note, miR-22-3p bound to and inhibited KDM6B, as demonstrated by dual-luciferase reporter gene assay and Western blot assay. Overexpression of KDM6B enhanced apoptosis of neurons in the OGD/RP model, and KDM6B bound to BMB2 and promoted its expression by binding to BMP2. Silencing of BMF reduced infarct volume and apoptosis in the stroke model. Conclusion Results support a conclusion that ASC-EV-derived miR-22-3p could alleviate brain ischemic injury by inhibiting KDM6B-mediated effects on the BMP2/BMF axis. These findings compelling indicate a novel treatment strategy for cerebral ischemic injury.

show abstract

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

Cited by 53 publications

References 118 publications

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

Traumatic brain injury

Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis

Contact Info

Product

Resources

About