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MCC950 regulates stem cells destiny through modulating SIRT3-NLRP3 inflammasome dynamics during oxygen glucose deprivation-induced oxidative and inflammatory stress
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Prakash, R., Kumari, N., Siddiqui, A. J., Khan, A. Q., Khan, M. A., Khan, R., Haque, R., Robertson, A. A. B., Boltze, Johannes and Raza, S. S. (2023) MCC950 regulates stem cells destiny through modulating SIRT3-NLRP3 inflammasome dynamics during oxygen glucose deprivation-induced oxidative and inflammatory stress. Stem Cell Reviews and Reports . doi:10.1007/s12015-023-10520-6 ISSN 2629-3277. (In Press)
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WRAP-MCC950-regulates-stem-cells-destiny-modulating-SIRT3-NLRP3-23.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only until 22 February 2024. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (2863Kb) |
Official URL: https://doi.org/10.1007/s12015-023-10520-6
Abstract
Ischemic stroke is the major cause of death and morbidity worldwide. Stem cell treatment is at the forefront of ischemic therapeutic interventions. However, the fate of these cells following transplantation is mostly unknown. The current study examines the influence of oxidative and inflammatory pathological events associated with experimental ischemic stroke (oxygen glucose deprivation (OGD)) on the stem cell population (human Dental Pulp Stem Cells, and human Mesenchymal Stem Cells) through the involvement of the NLRP3 inflammasome. We explored the destiny of the above-mentioned stem cells in the stressed micro (-environment) and the ability of MCC950 to reverse the magnitudes. An enhanced expression of NLRP3, ASC, cleaved caspase1, active IL-1β and active IL-18 in OGD-treated DPSC and MSC was observed. The MCC950 significantly reduced NLRP3 inflammasome activation in the aforementioned cells. Further, in OGD groups, oxidative stress markers were shown to be alleviated in the stem cells under stress, which was effectively relieved by MCC950 supplementation. Interestingly, whereas OGD increased NLRP3 expression, it decreased SIRT3 levels, implying that these two processes are intertwined. In brief, we discovered that MCC950 inhibits NLRP3-mediated inflammation by inhibiting the NLRP3 inflammasome and increasing SIRT3. To conclude, according to our findings, inhibiting NLRP3 activation while enhancing SIRT3 levels with MCC950 reduces oxidative and inflammatory stress in stem cells under OGD-induced stress. These findings shed light on the causes of hDPSC and hMSC demise following transplantation and point to strategies to lessen therapeutic cell loss under ischemic-reperfusion stress.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RB Pathology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Library of Congress Subject Headings (LCSH): | Cerebral ischemia, Cerebrovascular disease , Stem cells, Dental pulp, Mesenchymal stem cells , Stem cells -- Therapeutic use, Inflammation -- Immunological aspects | ||||||
| Journal or Publication Title: | Stem Cell Reviews and Reports | ||||||
| Publisher: | Springer | ||||||
| ISSN: | 2629-3277 | ||||||
| Official Date: | 22 February 2023 | ||||||
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| DOI: | 10.1007/s12015-023-10520-6 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | In Press | ||||||
| Reuse Statement (publisher, data, author rights): | “This version of the article has been accepted for publication, after peer review (when applicable) but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s12015-023-10520-6. Use of this Accepted Version is subject to the publisher’s Accepted Manuscript terms of use https://www.springernature.com/gp/open-research/policies/acceptedmanuscript-terms”." | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| Date of first compliant deposit: | 22 February 2023 | ||||||
| RIOXX Funder/Project Grant: |
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