MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system

Wang, Tian; Jian, Zhe; Baskys, Andrius; Jun, Yang; Li, Jianying; Guo, Hua; Hei, Yue; Xian, Panpan; He, Zhongzheng; Li, Zhengyu; Li, Namiao; Long, Qianfa

doi:10.1016/j.biomaterials.2020.120264

Cited by 145 publications

(131 citation statements)

References 56 publications

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“…Taking this into consideration, examination of the oxidative defense system may reveal the mechanism(s) underlying MSC-EXO therapeutic action on hippocampal neurons in AD. Furthermore, our previous study indicated that MSC-EXO show antioxidant activity as they contained enriched functional agents such as nucleic acids, proteins and enzymes that regulate redox reactions [23]. Antioxidants also have great potential in the treatment of neurodegenerative diseases and have been shown to improve learning and memory de cits in AD mice [57,58].…”

Section: Discussionmentioning

confidence: 99%

“…MSCs were obtained via enzymatic digestion of Wharton's jelly within the umbilical cord and expanded using standard medium, α-minimum essential medium (α-MEM; Gibco, New York, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, New York, USA), 100 U/mL penicillin and 100 μg/ mL streptomycin (Gibco, New York, USA) as previously described [23].…”

Section: Mscs Culture and Ow Cytometry (Fcm) Identi Cationmentioning

confidence: 99%

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WITHDRAWN: Amelioration of hippocampal neuronal morphology and function by mesenchymal stem cell-derived exosomes in APP/PS1 transgenic mice

Wang

Liu

et al. 2021

Preprint

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Mesenchymal stem cell-derived exosomes (MSC-EXO), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the therapeutic effects and underlying mechanism(s) of MSC-EXO in Alzheimer's disease (AD) are not well understood. The aim of this study was to investigate the action of MSC-EXO on hippocampal neuronal structure and function in APPswe/PS1dE9 (APP/PS1) transgenic mice. Here, the APP/PS1 transgenic mice received a single-dose of MSC-EXO via a tail vein injection, and were then assessed for pathological changes, neuronal morphology alterations, electrophysiological variations, and behavioral deficits. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of oxidative injury) signaling pathway was probed by Western blotting in H2O2-stimulated hippocampal neurons and a mouse model of AD. Our results showed that MSC-EXO therapy inhibited β-amyloid protein (Aβ) aggregation by reducing protein expression of 6E10 (marker of deposited amyloid plaques), repaired the synapses and dendritic spines of hippocampal neurons, restored action potentials in hippocampal pyramidal cells, improved cognitive abilities, and reduced memory impairments in a mouse model of AD. Additionally, we found that the Nrf2 signaling pathway participated in the actions of MSC-EXO, both in vitro and in vivo. Together, these data indicate that MSC-derived exosomes ameliorate the deficits in hippocampal neuronal structure and function associated with the Nrf2 signaling pathway in APP/PS1 transgenic mice, suggesting the MSC-EXO as a functional therapeutic agent in AD.

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Section: Discussionmentioning

confidence: 99%

Section: Mscs Culture and Ow Cytometry (Fcm) Identi Cationmentioning

confidence: 99%

WITHDRAWN: Amelioration of hippocampal neuronal morphology and function by mesenchymal stem cell-derived exosomes in APP/PS1 transgenic mice

Wang

Liu

et al. 2021

Preprint

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“…Exosomes are the nanosized membrane-bound delivery vesicles, which play a critical role in regulating cellular biofunction by mediating cell-to-cell communication. Mesenchymal stem cellderived exosomes protect skin from oxidative stress-induced skin damage through adaptive regulation of Nrf2 defense system [47]. Exosomes extracted from mesenchymal stem cell ameliorate cardiomyocyte apoptosis through by miR-144 targeting the PTEN/AKT pathway [48].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Derived microRNAs in Sertoli Cells Inhibit Spermatogonial Apoptosis

Gao¹,

Cao²,

Jin³

et al. 2021

Preprint

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BackgroundSpermatogenesis is a highly complicated biological process that occurs in the epithelium of the seminiferous tubules. It is regulated by a complex network of endocrine and paracrine factors and juxtacrine testicular cross-talk . Sertoli cells (SCs) play a key role in spermatogenesis due to their production of trophic, differentiation and immune-modulating factors. However, many of the molecular pathways of SCs action remain controversial and unclear. Recently, research has focused on exosomes as an important mechanism of intercellular communication. ResultsW e found that the exosomes derived from SCs ( SC-Exos ) significantly inhibited the apoptosis of the primary spermatogonial stem cells (SSCs). Total of 1016 miRNAs in SCs and 556 miRNAs in SC-Exos were detected using microRNA (miRNA) high-throughput sequencing. Further, 294 miRNAs were differentially expressed between SCs and SC-Exos. Based on the GO and KEGG analyses, the target genes of 37 (high-expressed in exosomes and RPM>1000) selected miRNAs were involved in multiple biological pathw ays, including the MAPK signaling pathway and PI3K/AKT signaling pathway. And miR-10b is one of the top ten exosomes with relatively large enrichment of microRNA. In addition, the overexpression of miR-10b down-regulated expression of the target KLF4 to reduce spermatogonial apoptosis in SSCs or C18-4 cell line. ConclusionsThe study indicated a large number of small RNAs loaded in exosomes was secreted form the donor SCs to target spermatogonial regulated the apoptosis. And miR-10b inhibits the apoptosis of spermatogonia through the target gene KLF4.

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“…Previous studies have reported that MSCs play a key role in alleviating DNA damage and oxidative stress damage [97]. MSC-exosomes, the functional role of which depend on their cargo derived from cells of origin, exert similar remodeling effects [98][99][100]. For example, in an oxidative stress-induced skin injury model, MSC-exosome treatment decreased ROS generation and subsequent DNA damage and improved the antioxidant capacities of damaged cells through NRF2 signaling [100].…”

Section: Role Of Msc-exosomes In Repairing Radiation Damagementioning

confidence: 99%

“…MSC-exosomes, the functional role of which depend on their cargo derived from cells of origin, exert similar remodeling effects [98][99][100]. For example, in an oxidative stress-induced skin injury model, MSC-exosome treatment decreased ROS generation and subsequent DNA damage and improved the antioxidant capacities of damaged cells through NRF2 signaling [100]. Other studies have found that after MSC-exosome treatment in an ischemic renal disease model, damaged renal cells showed reduced oxidative stress marker (MDA) levels, increased anti-oxidant marker (SOD and CAT) levels, and significantly reduced DNA damage parameters [98].…”

Section: Role Of Msc-exosomes In Repairing Radiation Damagementioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Gao

et al. 2020

Cells

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Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

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MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system

Cited by 145 publications

References 56 publications

WITHDRAWN: Amelioration of hippocampal neuronal morphology and function by mesenchymal stem cell-derived exosomes in APP/PS1 transgenic mice

WITHDRAWN: Amelioration of hippocampal neuronal morphology and function by mesenchymal stem cell-derived exosomes in APP/PS1 transgenic mice

Exosome-Derived microRNAs in Sertoli Cells Inhibit Spermatogonial Apoptosis

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

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