Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression

Peng, Hao; Liang, Zhanhua; Piao, Hong‐Guang; Ji, Xiaofei; Wang, Yachen; Liu, Yong; Liu, Rutao; Liu, Jing

doi:10.1007/s11011-014-9490-y

Cited by 62 publications

(41 citation statements)

References 64 publications

(83 reference statements)

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“…The resulting accumulation of extracellular glutamate together with the increased susceptibility of infants to its cytotoxic effects play a central role in the pathophysiology of HIE. Glutamate antagonists have been shown to potently reduce neuronal cell death in vitro as well in vivo by various mechanisms, including TNFa inhibition by NFkB, reduction of reactive oxygen species, and regulation of energy metabolism [36][37][38][39][40][41][42]. In our study, OGD led to a drastic increase of glutamate levels in the supernatant of brain slices, which stayed elevated for days after the injury.…”

Section: Figsupporting

confidence: 52%

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact

Sweda

Phillips

Marx

et al. 2016

Stem Cells and Development

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Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration.

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Section: Figsupporting

confidence: 52%

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact

Sweda

Phillips

Marx

et al. 2016

Stem Cells and Development

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“…The optimal protective effect of the CM as reported is 50%. Diminished effect is observed when CM concentrations lower than 50 % and 70% is used [Hao et al, ]. ADSCs are shown to be good for bone regeneration and the amount and quality of the bone regenerated show similar results, when compared to the conditioned media [Urayama and Banks, ].…”

Section: Discussionmentioning

confidence: 99%

Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models

Shree

Bhonde

2017

J. Cell. Biochem.

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The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc.

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“…Measurement of ATP content. Isolated mitochondria (n=6 animals per group) were used to measure ATP synthesis with a luciferase/luciferin-based system as previously described (19). The ATP Assay kit (cat.…”

Section: Mri Studymentioning

confidence: 99%

Exogenous carbon monoxide protects against mitochondrial DNA‑induced hippocampal pyroptosis in a model of hemorrhagic shock and resuscitation

Zhang

et al. 2020

Int J Mol Med

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carbon monoxide-releasing molecule-3 (cORM-3), which is an exogenous carbon monoxide (cO) compound, slowly releases cO under physiological conditions; this exerts neuroprotective effects against incomplete ischemia/reperfusion injury. The objective of the present study was to investigate whether the administration of cORM-3 protects against nucleotide-binding oligomerization domain-like receptor pyrin domain-3 (NLRP3) inflammasome formation and neuronal pyroptosis in the hippocampus following hemorrhagic shock and resuscitation (HSR). To establish this, an HSR model was created. Hemorrhagic shock was induced in adult male Sprague-Dawley rats under sevoflurane anesthesia by bleeding using a heparinized syringe to maintain a mean arterial pressure of 30±5 mmHg for 60 min. Resuscitation was performed by reperfusion of the blood and, if necessary, administering sterile saline to achieve the baseline arterial pressure. Following resuscitation, cORM-3 (4 mg/kg) was injected via the femoral vein. Neuronal pyroptosis in the hippocampus, mitochondrial morphology, mitochondrial dNA (mtdNA), brain magnetic resonance imaging, expression levels of NLRP3 and the interaction of pro-caspase-1 and apoptosis-associated speck-like protein containing a cARd domain (ASc) were examined 12 h after HSR; locomotor activity was assessed 7 days after HSR. compared with HSR-treated rats, cORM-3 administration resulted in a lower level of neuronal pyroptosis in the hippocampus, improved mitochondrial morphology, a lower mtdNA level, steadier levels of metabolites, decreased expression levels of NLRP3 and pro-caspase-1 interacting with ASc and enhanced locomotor activity. In conclusion, treatment with cORM-3 ameliorated impairments of locomotor and exploratory activities in a rat model of HSR. The mechanism may be associated with the inhibition of mitochondrial dNA-induced pyroptosis via improvements in cell metabolism.Abbreviations: cORM, carbon monoxide-releasing molecule; HSR, hemorrhage shock and resuscitation; NLRP3, nucleotide-binding oligomerization domain-like receptors pyrin domain-3; MRS, magnetic resonance spectroscopy

show abstract

Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression

Cited by 62 publications

References 64 publications

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact

Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models

Exogenous carbon monoxide protects against mitochondrial DNA‑induced hippocampal pyroptosis in a model of hemorrhagic shock and resuscitation

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