Enhancement of Mitochondrial Transfer by Antioxidants in Human Mesenchymal Stem Cells

Li, Chia-Jung; Chen, Po-Kong; Sun, Li; Pang, Cheng‐Yoong

doi:10.1155/2017/8510805

Cited by 43 publications

(25 citation statements)

References 30 publications

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“…The transfer of proteins from stromal cells to leukemic cells may significantly support the resistance to treatment and contribute to disease progression. Such protein transfer to increase cytoprotection, in addition to the transfer of mitochondria from healthy cells to damaged cells in monotypic and heterotypic biological setups, likely increases the survival of recipient cells (Li et al, 2017;Sanchez et al, 2017;Wang & Gerdes, 2015;Pasquier et al, 2013). Altogether, our data confirmed the general role of direct intercellular cargo transfer as a supportive and protective mechanism.…”

Section: Discussionsupporting

confidence: 77%

Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

Kolba

Dudka

Zaręba-Kozioł

et al. 2018

Preprint

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Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous protrusions that enable the direct transfer of various cargo between cells. Here we show that TNTs are formed between leukemic and bone marrow stromal cells. Fluorescence confocal microscopy with 3D reconstructions, correlative light-electron microscopy and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated that the stromal cells stimulate TNT-mediated vesicle transfer towards leukemic cells. Transfer of vesicular cargo from stromal cells correlated with increased resistance to anti-leukemic treatment. Moreover, specific sets of proteins with a potential role in survival and the drug response were transferred within these vesicles. Altogether, we found that TNTs are involved in the leukemia-stroma cross-talk and the stroma-mediated cytoprotection of leukemic cells. Our findings implicate TNT connections as a possible target for therapeutic interventions within the leukemia microenvironment to attenuate stroma-conferred protection.

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Section: Discussionsupporting

confidence: 77%

Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

Kolba

Dudka

Zaręba-Kozioł

et al. 2018

Preprint

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“…However, NAC has also been demonstrated to inhibit adipocyte differentiation and to maintain the osteogenic differentiation capacity of MSCs by decreasing ROS levels . Moreover, a combination of NAC and L‐ascorbic acid 2‐phosphate promoted the growth of MSCs and suppressed oxidative stress‐induced cell death by enhancing mitochondrial integrity and function in vitro under H 2 O 2 ‐induced oxidative stress . Preconditioning with Vitamin E eliminates H 2 O 2 ‐induced injury in MSCs in vitro, and transplantation of these pretreated MSCs increases the proteoglycan content of cartilage matrix for tissue repair of osteoarthritis in vivo .…”

Section: Strategies To Control Ros Levels For Msc Fates In Vitro Andmentioning

confidence: 99%

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Zhao

Peng

et al. 2018

J Cellular Molecular Medi

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Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.

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“…Data represents the mean ± SEM of 3 independent experiments with n > 80 neurons for each group. Two-way ANOVA: cisplatin x transfected astrocyte interaction: (****p < 0.0001), followed by Tukey's post-hoc test (****p < 0.0001) like lysosomes, and last but not least, mitochondria [17,43,44]. Multiple authors have described that the mitochondrial Rho-GTPase-1 protein (Miro-1) is a crucial player in intercellular mitochondrial transfer via TNTs.…”

Section: Discussionmentioning

confidence: 99%

Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer

English

Shepherd

Uzor

et al. 2020

acta neuropathol commun

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Neurodegenerative disorders, including chemotherapy-induced cognitive impairment, are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health. We used an in vitro system in which astrocytes containing mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons damaged by cisplatin. Culture of primary cortical neurons with cisplatin reduced neuronal survival and depolarized neuronal mitochondrial membrane potential. Cisplatin induced abnormalities in neuronal calcium dynamics that were characterized by increased resting calcium levels, reduced calcium responses to stimulation with KCl, and slower calcium clearance. The same dose of cisplatin that caused neuronal damage did not affect astrocyte survival or astrocytic mitochondrial respiration. Co-culture of cisplatin-treated neurons with astrocytes increased neuronal survival, restored neuronal mitochondrial membrane potential, and normalized neuronal calcium dynamics especially in neurons that had received mitochondria from astrocytes which underlines the importance of mitochondrial transfer. These beneficial effects of astrocytes were associated with transfer of mitochondria from astrocytes to cisplatin-treated neurons. We show that siRNA-mediated knockdown of the Rho-GTPase Miro-1 in astrocytes reduced mitochondrial transfer from astrocytes to neurons and prevented the normalization of neuronal calcium dynamics. In conclusion, we showed that transfer of mitochondria from astrocytes to neurons rescues neurons from the damage induced by cisplatin treatment. Astrocytes are far more resistant to cisplatin than cortical neurons. We propose that transfer of functional mitochondria from astrocytes to neurons is an important repair mechanism to protect the vulnerable cortical neurons against the toxic effects of cisplatin.

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Enhancement of Mitochondrial Transfer by Antioxidants in Human Mesenchymal Stem Cells

Cited by 43 publications

References 30 publications

Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer

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