Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity
Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have sho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/1/93 |
| _version_ | 1827371312996155392 |
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| author | Sawdah A. Ali Dinender K. Singla |
| author_facet | Sawdah A. Ali Dinender K. Singla |
| author_sort | Sawdah A. Ali |
| collection | DOAJ |
| description | Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study, H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (<i>p</i> < 0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data show that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy. |
| first_indexed | 2024-03-08T10:38:28Z |
| format | Article |
| id | doaj.art-7f2d69f600e94ebba69a18da725e2fe9 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T10:38:28Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7f2d69f600e94ebba69a18da725e2fe92024-01-26T18:06:01ZengMDPI AGPharmaceuticals1424-82472024-01-011719310.3390/ph17010093Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced CardiotoxicitySawdah A. Ali0Dinender K. Singla1Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USADoxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study, H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (<i>p</i> < 0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data show that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.https://www.mdpi.com/1424-8247/17/1/93MSC-ExosDOXpyroptosisinflammation |
| spellingShingle | Sawdah A. Ali Dinender K. Singla Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity Pharmaceuticals MSC-Exos DOX pyroptosis inflammation |
| title | Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity |
| title_full | Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity |
| title_fullStr | Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity |
| title_full_unstemmed | Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity |
| title_short | Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity |
| title_sort | mesenchymal stem cell derived exosomes ameliorate doxorubicin induced cardiotoxicity |
| topic | MSC-Exos DOX pyroptosis inflammation |
| url | https://www.mdpi.com/1424-8247/17/1/93 |
| work_keys_str_mv | AT sawdahaali mesenchymalstemcellderivedexosomesamelioratedoxorubicininducedcardiotoxicity AT dinenderksingla mesenchymalstemcellderivedexosomesamelioratedoxorubicininducedcardiotoxicity |