Neural stem cells traffic functional mitochondria via extracellular vesicles

Peruzzotti-Jametti, ﻿Luca; Bernstock, Joshua D.; Willis, Cory M.; Manferrari, Giulia; Rogall, Rebecca; Fernández-Vizarra, Erika; Williamson, James C; Braga, Alice; Bosch, Aletta van den; Leonardi, Tommaso; Krzak, Grzegorz; Kittel, Ágnes; Benincá, Cristiane; Vicario, Nunzio; Tan, Sisareuth; Bastos, Carlos; Bicci, Iacopo; Iraci, Nunzio; Smith, JA; Peacock, Ben; Müller, Karin H.; Lehner, Paul J.; Buzás, Edit I.; Faria, Nuno; Zeviani, Massimo; Frezza, Christian; Brisson, Alain; Matheson, Nicholas J; Viscomi, Carlo; Pluchino, ﻿Stefano

doi:10.1371/journal.pbio.3001166

Cited by 109 publications

(96 citation statements)

References 84 publications

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“…However, the biological activity of natural protein cargo has been assessed only in a few cases and requires sophisticated transgenic experimental setups, as exemplified in the case of Ferritin heavy chain transfer to neurons via oligodendrocyte‐derived EVs 54 or the delivery of NADPH‐oxidase‐2 from macrophages to injured neurons facilitating neuronal regeneration after lesion through ROS generation 72 . Intriguingly, during nervous system regeneration after injury or under inflammatory conditions, even larger organelles such as ribosomes or mitochondria may be transferred via EVs 73,74 …”

Section: Cargo Of Neural Evs: How Do They Act?mentioning

confidence: 99%

Extracellular Vesicles in neural cell interaction and CNS homeostasis

et al. 2021

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Central nervous system (CNS) homeostasis critically depends on the interaction between neurons and glia cells. Extracellular vesicles (EVs) recently emerged as versatile messengers in CNS cell communication. EVs are released by neurons and glia in activity-dependent manner and address multiple target cells within and outside the nervous system. Here, we summarize the recent advances in understanding the physiological roles of EVs in the nervous system and their ability to deliver signals across the CNS barriers. In addition to the disposal of cellular components via EVs and clearance by phagocytic cells, EVs are involved in plasticity-associated processes, mediate trophic support and neuroprotection, promote axonal maintenance, and modulate neuroinflammation. While individual functional components of the EV cargo are becoming progressively identified, the role of neural EVs as compound multimodal signaling entities remains to be elucidated. Novel transgenic models and imaging technologies allow EVtracking in vivo and provide further insight into EV targeting and their mode of action. Overall, EVs represent key players in the maintenance of CNS homeostasis essential for the life-long performance of neural networks and thus provide a wide spectrum of biomedical applications.

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Section: Cargo Of Neural Evs: How Do They Act?mentioning

confidence: 99%

Extracellular Vesicles in neural cell interaction and CNS homeostasis

et al. 2021

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“…This mechanism is strictly dependent on the altered function of extracellularly released mitochondria, as intact extracellular astrocytic mitochondria instead provide neuroprotection (127)(128)(129). Recent work from our group has shown that delivering functional extracellular mitochondria (via extracellular vesicles) is effective in re-establishing normal mitochondrial function in myeloid cells in vitro and in vivo during neuroinflammation (130). Further studies will be needed to identify the applicability of these findings to the cure of progressive MS and other neurodegenerative disorders (131).…”

Section: Mitochondrial Dynamics In Myeloid Cellsmentioning

confidence: 99%

Metabolic Control of Smoldering Neuroinflammation

et al. 2021

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Compelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation.

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“…More importantly, the traffic of functional mitochondria was also recently shown to occur in NSCs via extracellular vesicles. For the first time, Peruzzotti-Jametti et al have demonstrated that transfer of mitochondria from NSC-derived EVs rescues mitochondrial function and cell survival in mtDNA-deficient target cells [133].…”

Section: Antioxidative Potential Of Delivered Extracellular Vesicles and Tunneling Nanotubesmentioning

confidence: 99%

“…For example, neurotrophic factors can either promote the expression and activity of antioxidant enzymes, allowing a direct scavenge of free radicals; or directly act on mitochondria, enhancing their functioning or preventing their impairment. Notably, recent findings have also suggested that EVs delivered by NSCs are a source of proteins involved in cellular protection against oxidative stress and, importantly, also carry functional mitochondria to rescue respiration and cell survival in recipient cells [133]. Surely, this is an interesting point to further explore in the future, once it represents an innovative mechanism to improve endogenous NSC protection throughout life.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

2021

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The adult mammalian brain is capable of generating new neurons from existing neural stem cells (NSCs) in a process called adult neurogenesis. This process, which is critical for sustaining cognition and mental health in the mature brain, can be severely hampered with ageing and different neurological disorders. Recently, it is believed that the beneficial effects of NSCs in the injured brain relies not only on their potential to differentiate and integrate into the preexisting network, but also on their secreted molecules. In fact, further insight into adult NSC function is being gained, pointing to these cells as powerful endogenous “factories” that produce and secrete a large range of bioactive molecules with therapeutic properties. Beyond anti-inflammatory, neurogenic and neurotrophic effects, NSC-derived secretome has antioxidant proprieties that prevent mitochondrial dysfunction and rescue recipient cells from oxidative damage. This is particularly important in neurodegenerative contexts, where oxidative stress and mitochondrial dysfunction play a significant role. In this review, we discuss the current knowledge and the therapeutic opportunities of NSC secretome for neurodegenerative diseases with a particular focus on mitochondria and its oxidative state.

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Neural stem cells traffic functional mitochondria via extracellular vesicles

Cited by 109 publications

References 84 publications

Extracellular Vesicles in neural cell interaction and CNS homeostasis

Extracellular Vesicles in neural cell interaction and CNS homeostasis

Metabolic Control of Smoldering Neuroinflammation

Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

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