Exosomes Derived from Human Amniotic Fluid Mesenchymal Stem Cells Preserve Microglia and Neuron Cells from Aβ

Abstract

Background: Neuroinflammation is involved in neuronal cell death that occurs in neurodegenerative diseases such as Alzheimer’s disease (AD). Microglia play important roles in regulating the brain amyloid beta (Aβ) levels, so immunomodulatory properties exerted by mesenchymal stem cells may be exploited to treat this pathology. The evidence suggests that the mechanism of action of human amniotic fluid stem cells (hAFSCs) is through their secretome, which includes exosomes (exo). Methods: We examined the effect of exosomes derived from human amniotic fluid stem cells (hAFSCs-exo) on activated BV-2 microglia cells by lipopolysaccharide (LPS) as a neuroinflammation model. To investigate the exo effect on the interplay between AD neurons and microglia, SH-SY5Y neuroblastoma cells treated with Aβ were exposed to a conditioned medium (CM) obtained from activated BV-2 or co-culture systems. Results: We found that the upregulation of the markers of pro-inflammatory microglia was prevented when exposed to hAFSC-exo whereas the markers of the anti-inflammatory macrophage phenotype were not affected. Interestingly, the hAFSC-exo pretreatment significantly inhibited the oxidative stress rise and apoptosis occurring in the neurons in presence of both microglia and Aβ. Conclusion: We demonstrated that hAFSC-exo mitigated an inflammatory injury caused by microglia and significantly recovered the neurotoxicity, suggesting that hAFSC-exo may be a potential therapeutic agent for inflammation-related neurological conditions, including AD.

Exosomes in brain diseases: Pathogenesis and therapeutic targets

“…A study was conducted to investigate the effect of exosomes on the SH‐SY5Y interaction between AD neurons and microglia. The results demonstrated that hAFSC‐Exos could inhibit the inflammatory response, oxidative stress, and microglial apoptosis and could be a potential therapeutic drug for diseases related to inflammation such as AD in the future 195 …”

“…The results demonstrated that hAFSC-Exos could inhibit the inflammatory response, oxidative stress, and microglial apoptosis and could be a potential therapeutic drug for diseases related to inflammation such as AD in the future. 195 Neuroinflammation is associated with neuronal cell death in AD. Coenzyme Q10 (CoQ10), as a supplement to anti-inflammatory and antioxidant stress, can improve AD-related inflammation and oxidative stress.…”

Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia

“…Some in vitro and in vivo recent studies demonstrated the applicability of exosomes derived from stem cells (SCs) for therapeutic purposes. The SC-derived exosomes have demonstrated the potential to treat many diseases and disorders including neurodegenerative diseases [ 178 , 179 ], cardiovascular ischemia [ 180 , 181 , 182 ], osteoporosis and osteoarthritis [ 183 , 184 ], and kidney and liver diseases [ 185 , 186 ]. EV-based therapy represents a highly potent cell-free therapy approach.…”

Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia

“…EVs derive from MSCs and anti-inflammatory immune cells that can reduce the inflammatory damage and cell stress ( Thome et al, 2022 ). The exosomes of human amniotic fluid MSCs can treat the inflammation-related neurological diseases by reducing inflammation caused by microglia and improving neurotoxicity ( Zavatti et al, 2022 ). EV-mediated the delivery of DnaJ Homolog Subfamily B Member 6 (DNAJB6) molecular chaperone inhibits the aggregation of polyQ and HTT proteins to delay the onset of HD ( Joshi et al, 2021 ).…”