Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats

Abstract

The goal of the current study was to investigate the therapeutic effects of exosomes derived from mesenchymal stem cells (MSCs-Exo) and copper sulfide nanoparticles (CuSNPs) as biomaterials in order to understand the mechanisms that contribute to overcoming cadmium (Cad) induced neurological disorders in rats. Animals were divided into five groups (n = 10): group 1 was served as a negative control and receive vehicle saline (Con), group 2 Positive control groups were received Cad as cadmium chloride at a dose of 20 mg/kg/day for six weeks (Cad group), group 3 was received Cad plus MSCs-Exo as a single dose of 100 μLi. v. (Cad + MSCs-Exo), group 4 was received Cad plus CuSNPs at a dose of 6.5 mg/kg orally (Cad + CuSNPs), group 5 was received Cad + MSCs-Exo + CuSNPs for six weeks. However, the activities of each acetylcholine (Ach), acetylcholinesterase (AchE), total antioxidant status (TAC) were measured. Also, the levels of ROS, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), Brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were evaluated. Beneficial effects on the behavior of animals were observed after treatment with MSCs-Exo and CuSNPs. Furthermore, the administration of MSCs-Exo and CuSNPs have been improve the TAC, BDNF and NGF via ameliorating the oxidative stress and inflammatory markers. Moreover, Histopathological studies had shown that great development in the brain of Cad rats treated with MSCs-Exo and CuSNPs. In conclusion, this study offers an overview of innovative stem cell therapy techniques and how to integrate them with nanotechnology to boost therapeutic performance.

Combined Effects of Cadmium- and Cyanide-Contaminated Diet on Oxidative Stress Biomarkers in Different Tissues of Rats

“…Previous reports have demonstrated that the production of free radicals is, to some extent, associated with changes in AChE activity in the brain [54,55]. The findings of the current study showing the inhibition of AChE activity in the brain exerted by Cd and CN confirm the observations of previous studies suggesting that the inactivation of AChE enzymes is due to the occupation of its active sites by pollutants [56,57].…”

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

“…In Zaazaa's proof‐of‐concept animal study, BM MSC‐derived sEVs were coupled with copper sulfide nanoparticles, acting as neuroprotective agents. [ 106 ] This system improved cholinergic function in the brain tissue of cadmium‐treated rats and reduced oxidative stress and inflammation by upregulating nerve growth factor and BDNF while downregulating TNF‐α & NF‐κB.…”

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

“…Furthermore, Cd exposure may contribute to AD due to degenerative brain alterations [ 220 ]. In a recent study investigating the potential of NPs and exosomes to ameliorate neurological disorders, copper sulfide NPs and MSC-derived exosomes were co-delivered to rats in a Cd-induced neurological disorder model [ 221 ]. Improved anticholinesterase, antioxidant, and anti-inflammatory responses were observed after IV injection of MSC-derived exosomes and copper sulfide NPs.…”

“…Improved anticholinesterase, antioxidant, and anti-inflammatory responses were observed after IV injection of MSC-derived exosomes and copper sulfide NPs. Histological evaluations revealed that treatment with MSC-derived exosomes and copper sulfide NPs decreased the toxic effects of Cd on brain tissue and reduced degenerative alterations originating from neuronal disorders [ 221 ]. Future investigations should evaluate the applications of exosomal-membrane-coated NPs in the delivery of biomaterials, drugs, and genes.…”