Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

Jiang, Dan; Gao, Fei; Zhang, Yuelin; Wong, David; Li, Qing; Tse, Hung‐Fat; Xu, Goufeng; Yu, Zhen; Lian, Qizhou

doi:10.1038/cddis.2016.358

Cited by 187 publications

(138 citation statements)

References 33 publications

(41 reference statements)

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“…In accordance, our previous studies have demonstrated that indirect transwell MSC‐islet coculture does not improve GSIS, in contrast to the robust improvements we have consistently observed using direct contact coculture of islets with MSCs. Several mechanisms of mitochondria transfer from MSCs to injured tissues have been proposed, including microvesicles, TNTs, mitochondrial extrusion, and cytoplasmic fusion with the recipient cells (reviewed in Reference ). In a mouse model of acute lung injury, mitochondrial donation to alveolar epithelial cells was dependent on the stabilization of cell: cell adhesion via the establishment of Cx43‐containing GJCs and subsequent formation of mitochondria‐transferring TNTs .…”

Section: Discussionmentioning

confidence: 99%

Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer

et al. 2020

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Pretransplant islet culture is associated with the loss of islet cell mass and insulin secretory function. Insulin secretion from islet β‐cells is primarily controlled by mitochondrial ATP generation in response to elevations in extracellular glucose. Coculture of islets with mesenchymal stromal cells (MSCs) improves islet insulin secretory function in vitro, which correlates with superior islet graft function in vivo. This study aimed to determine whether the improved islet function is associated with mitochondrial transfer from MSCs to cocultured islets. We have demonstrated mitochondrial transfer from human adipose MSCs to human islet β‐cells in coculture. Fluorescence imaging showed that mitochondrial transfer occurs, at least partially, through tunneling nanotube (TNT)‐like structures. The extent of mitochondrial transfer to clinically relevant human islets was greater than that to experimental mouse islets. Human islets are subjected to more extreme cellular stressors than mouse islets, which may induce “danger signals” for MSCs, initiating the donation of MSC‐derived mitochondria to human islet β‐cells. Our observations of increased MSC‐mediated mitochondria transfer to hypoxia‐exposed mouse islets are consistent with this and suggest that MSCs are most effective in supporting the secretory function of compromised β‐cells. Ensuring optimal MSC‐derived mitochondria transfer in preculture and/or cotransplantation strategies could be used to maximize the therapeutic efficacy of MSCs, thus enabling the more widespread application of clinical islet transplantation.

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Section: Discussionmentioning

confidence: 99%

Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer

et al. 2020

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“…Extensive studies have confirmed that rotenone can induce oxidative damage in dopaminergic neurons, which exerts a key role in PD. Additionally, rotenone has also been shown to induce mitochondrial dysfunction (Yee et al, 2017), increase cytosolic free Ca 21 levels (Jiang et al, 2016), generate reactive oxygen species (ROS) (Brennan-Minnella et al, 2016), and elevate apoptotic proteins such as, Bax, caspase-3, and caspase-9 (Narasimhan et al, 2016). Furthermore, recent studies have demonstrated that rotenone could inhibit the mTOR signaling pathway (Liu et al, 2016), activate the glycogen synthase kinase-3 (GSK-3) signaling pathway (Gim enez-Cassina et al, 2012), and inhibit JNK and p38 MAPK signaling pathways (Park et al, 2014) leading to cell death or apoptosis.…”

Section: Abstract: Akt1; Neuroprotection; Resveratrol; Rotenone; Sirt1mentioning

confidence: 99%

Resveratrol Suppresses Rotenone‐induced Neurotoxicity Through Activation of SIRT1/Akt1 Signaling Pathway

Wang

Dong²,

Liu

et al. 2018

The Anatomical Record

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Rotenone is a common pesticide and has been reported as one of the risk factors for Parkinson disease. Rotenone can cause neuronal death or apoptosis through inducing oxidative injury and inhibiting mitochondrial function. As a natural polyphenolic compound, resveratrol possesses the antioxidant capacity and neuroprotective effect. However, the mechanism underlying the neuroprotective effect of resveratrol against rotenone-induced neurotoxicity remains elusive. Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH activity assays demonstrated that resveratrol could suppress neurotoxicity induced by rotenone (P < 0.01). The DCFH-DA assay indicated that resveratrol reduced the production of reactive oxygen species (ROS). JC-1 and Hoechst 33342/PI staining revealed that resveratrol attenuated mitochondrial dysfunction and cell apoptosis. Moreover, resveratrol reversed rotenone-induced decrease in SIRT1 expression and Akt1 phosphorylation (P < 0.05). Furthermore, when the SIRT1 and Akt1 activity was inhibited by niacinamide and LY294002, respectively, the neuroprotective effect of resveratrol was remarkably attenuated, which implied that SIRT1 and Akt1 could mediate this process and may be potential molecular targets for intervening rotenone-induced neurotoxicity. In summary, our study demonstrated that resveratrol reduced rotenone-induced oxidative damage, which was partly mediated through activation of the SIRT1/Akt1 signaling pathway. Our study launched a promising avenue for the potential application of resveratrol as a neuroprotective therapeutic agent in Parkinson disease. Anat Rec, 301:1115-1125, 2018. © 2018 Wiley Periodicals, Inc.

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“…This could imply that the formation of TNTs for intercellular transport is executed by astrocytes rather than neurons. Jiang et al (2016) have described that the cyclic ADP ribose hydrolase CD-38 plays an important role in astrocytic mitochondrial transfer. Inhibition of CD-38 with apigenin significantly reduced astrocytic mitochondrial transfer and it has been suggested that CD-38 may be involved in TNT formation (Marlein et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Astrocytes improve neuronal health after cisplatin treatment through mitochondrial transfer

English

Shepherd

Nzor³

et al. 2019

Preprint

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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 cocultured 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 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 those neurons that had received mitochondria from astrocytes. These beneficial effects of astrocytes were associated with transfer of mitochondria from astrocytes to cisplatin-treated neurons. The Rho-GTPase Miro-1 is known to contribute to mitochondrial motility and transfer. We show that siRNA-mediated knockdown of Miro-1 in astrocytes reduced mitochondrial transfer from astrocytes to neurons and prevented the normalization of neuronal calcium dynamics.In conclusion, we identified transfer of mitochondria from astrocytes to neurons damaged by cisplatin as an important repair mechanism to protect cortical neurons against the toxic effects of this chemotherapeutic. Significance statementChemotherapy-induced neurotoxicity is a serious health problem and little is known about the underlying mechanisms.Especially neurons are very sensitive to cisplatin treatment. We show that astrocytes can protect neurons damaged by cisplatin by improving neuronal survival, mitochondrial health, and calcium dynamics in vitro. This beneficial effect of astrocytes is dependent on the transfer of mitochondria from astrocytes to the damaged neurons. Our findings provide evidence for an important endogenous protective neuro-glial mechanism that could contribute to prevention of neuronal death as a result of cisplatin treatment and thereby aid in sustaining brain health of patients during chemotherapy.

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Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage

Cited by 187 publications

References 33 publications

Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer

Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer

Resveratrol Suppresses Rotenone‐induced Neurotoxicity Through Activation of SIRT1/Akt1 Signaling Pathway

Astrocytes improve neuronal health after cisplatin treatment through mitochondrial transfer

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