Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration

Abstract

Neurodegenerative diseases include a variety of pathologies such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and so forth, which share many common characteristics such as oxidative stress, glycation, abnormal protein deposition, inflammation, and progressive neuronal loss. The last century has witnessed significant research to identify mechanisms and risk factors contributing to the complex etiopathogenesis of neurodegenerative diseases, such as genetic, vascular/metabolic, and lifestyle-related factors, which often co-occur and interact with each other. Apart from several environmental or genetic factors, in recent years, much evidence hints that impairment in redox homeostasis is a common mechanism in different neurological diseases. However, from a pharmacological perspective, oxidative stress is a difficult target, and antioxidants, the only strategy used so far, have been ineffective or even provoked side effects. In this review, we report an analysis of the recent literature on the role of oxidative stress in Alzheimer’s and Parkinson’s diseases as well as in amyotrophic lateral sclerosis, retinal ganglion cells, and ataxia. Moreover, the contribution of stem cells has been widely explored, looking at their potential in neuronal differentiation and reporting findings on their application in fighting oxidative stress in different neurodegenerative diseases. In particular, the exposure to mesenchymal stem cells or their secretome can be considered as a promising therapeutic strategy to enhance antioxidant capacity and neurotrophin expression while inhibiting pro-inflammatory cytokine secretion, which are common aspects of neurodegenerative pathologies. Further studies are needed to identify a tailored approach for each neurodegenerative disease in order to design more effective stem cell therapeutic strategies to prevent a broad range of neurodegenerative disorders.

CRISPR/Cas9 Mediated Gene Modification Ameliorates Abnormal Phenotypes in SCA3/MJD Disease Patient Derived Induced Pluripotent Stem Cells

“…7a-b). Studies showed that abnormal changes in intracellular ROS and Ca 2+ levels were correlated with various neurodegenerative diseases [47][48][49][50]. In the present study, the ROS and intracellular Ca 2+ levels were signi cantly higher in SCA3/MJD-NCs compared with Ctr1-NCs, while obviously decreased in the corrected SCA3/MJD-NCs ( Fig.…”

“…The phenotypic abnormalities occurred in SCA3/MJD stem cell models were different from previous studies, which lay a valuable cellular models for pathological mechanism research. Altogether, these results may indicate that mutant ataxin3 could enhance Ca 2+ release from endoplasmic reticulum storages, then causing Ca 2+ overload and eventually cell death, accompanied by mitochondrial permeability, oxidative stress, cytoskeletal tissue destruction, and/or calpain activation [47][48][49][50].…”

“…Previous studies also indicated that mutant ataxin3 produced truncated C-terminal fragments in SCA3/MJD models after proteolysis, leading to increased mitochondrial division, decreased MMPs, increased ROS level and cell death [51,63]. Moreover, increased glutamate levels in synaptic cleft can activate receptors on neighboring neurons, contributing to the excessive and continuous increase of free Ca 2+ in neurons, thus promoting the vicious cycle of neuronal injury [48]. The phenotypic abnormalities occurred in SCA3/MJD stem cell models were different from previous studies, which lay a valuable cellular models for pathological mechanism research.…”

Neural-Induced Human Adipose Tissue-Derived Stem Cells Conditioned Medium Ameliorates Rotenone-Induced Toxicity in SH-SY5Y Cells

“…Considering the above information, it is crucial to develop treatments that can reduce α-syn aggregation and impede PD progression. Interestingly, cell-based therapies with mesenchymal stem cells (MSCs) and their secretomes have been shown to cross the BBB, which explains their use in the treatment of NDDs [ 16 ]. MSCs are self-renewing and multipotent progenitor cells, and their beneficial effects against NDDs were mainly due to the factors they secrete, rather than cellular engraftment in models of PD [ 17 , 18 ], demonstrating the neuroprotective ability of MSC-conditioned medium (MSCs-CM).…”

Combined Application Therapies of Stem Cells and Drugs in the Neurological Disorder Attenuation

“…SCs are obtained from the patient's own bone marrow and intravenously administered into the spinal cord. One year later, 30% epilepsy patients had a complete remission (without seizures), and 50% epilepsy patients who had not previously responded to the medication began to respond well [18][19][20].…”