Natural Compounds as a Strategy to Optimize “<i>In Vitro</i>” Expansion of Stem Cells

Maraldi, Tullia; Prata, Cecilia; Marrazzo, Pasquale; Hrelia, Silvana; Angeloni, Cristina

doi:10.1089/rej.2019.2187

Cited by 8 publications

(4 citation statements)

References 144 publications

(93 reference statements)

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“…In agreement with other authors [77,78,79], we suggest that a 3D culture system better mimics cell–cell interactions and cell–ECM interactions compared to the traditional 2D monolayer. In particular, our 3D model would be useful for future investigations of the neuroprotective activity of natural compounds [80]. In the present study, we observed the protective effect of an “acute” co-treatment with SF, EGCG, and PB but, taking into account the nature of neurodegeneration, a subchronic/chronic administration should be even more effective.…”

Section: Discussionmentioning

confidence: 55%

Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model

2019

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Currently, the majority of cell-based studies on neurodegeneration are carried out on two-dimensional cultured cells that do not represent the cells residing in the complex microenvironment of the brain. Recent evidence has suggested that three-dimensional (3D) in vitro microenvironments may better model key features of brain tissues in order to study molecular mechanisms at the base of neurodegeneration. So far, no drugs have been discovered to prevent or halt the progression of neurodegenerative disorders. New therapeutic interventions can come from phytochemicals that have a broad spectrum of biological activities. On this basis, we evaluated the neuroprotective effect of three phytochemicals (sulforaphane, epigallocatechin gallate, and plumbagin) alone or in combination, focusing on their ability to counteract oxidative stress. The combined treatment was found to be more effective than the single treatments. In particular, the combined treatment increased cell viability and reduced glutathione (GSH) levels, upregulated antioxidant enzymes and insulin-degrading enzymes, and downregulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 in respect to peroxide-treated cells. Our data suggest that a combination of different phytochemicals could be more effective than a single compound in counteracting neurodegeneration, probably thanks to a pleiotropic mechanism of action.

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Section: Discussionmentioning

confidence: 55%

Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model

2019

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“…They are a primary public health problem, affecting tens of millions of people worldwide [2]. Although their complex and endogenous antioxidant defense system [7], plays a key role in neurodegeneration as the brain is characterized by an elevated oxygen consumption, high levels of iron and copper, involved in ROS production, elevated content of polyunsaturated fatty acids, and low antioxidant defenses [1,8]. A schematic representation of causes and consequences of oxidative stress is shown in Figure 1.…”

Section: Oxidative Stress and Neurodegenerative Diseasesmentioning

confidence: 99%

“…These results suggest that neuronal therapeutic effect of stem cells is due to not only the release of essential neurotrophic factors, but also to the maintenance of an appropriate redox state that preserves neuronal function. Moreover, appropriate cell culture conditions are necessary to maintain the properties of stem cells ex vivo for clinical applications taking into consideration the fundamental role of the cellular redox status [7,167].…”

Section: Mesenchymal Stem Cells Contrast Neuronal Cell Damage Inducedmentioning

confidence: 99%

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

Angeloni

Gatti

Prata

et al. 2020

IJMS

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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.

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“…MSC cultivation in vitro often leads to a senescence process induction of these stem cells [ 134 ], so new easy strategies to counteract this event are needed [ 135 ]. Since an increase in ROS plays a key role in aging and apoptosis in mesenchymal stem cells derived from bone marrow (BMSCs), blocking NOX could enhance the anti-apoptotic and anti-aging ability of BMSCs counteracting oxidant stress, and thus improving their therapeutic efficacy.…”

Section: Noxs and Msc Application: The Fine Tuning Among Survival Proliferation Differentiation And Senescencementioning

confidence: 99%

NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

et al. 2021

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One of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative.

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Natural Compounds as a Strategy to Optimize “In Vitro” Expansion of Stem Cells

Cited by 8 publications

References 144 publications

Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model

Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model

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

NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

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