NLRP3 Inflammasome Inhibition of OP9 Cells Enhance Therapy for Inflammatory Bowel Disease

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Jul 24

PMID 37483815

Authors

Yutong Chen

Weicheng Meng

Guangming Ren

Ning An

Jing Zhang

Zhixin Liu

Xiaoshuang Wu

Wen Yin

Xingbin Hu

Zheng Liu

Fan Feng

Yaozhen Chen

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) are becoming more popular in therapy. Therefore, in-depth studies on mesenchymal stem cells in therapy are urgently needed. However, the difficulty in culturing and propagating MSCs complicates potential studies on MSCs in a murine model. OP9 cells are a stromal cell line from mouse bone marrow, which have similar characteristics and functions to MSCs and can maintain their original characteristics. Because of these properties, OP9 cells have become a suitable substitute for research on MSCs. Previously, we have found that MSCs can cure inflammatory bowel disease in mice. In this study, we aimed to investigate whether OP9 cells can functionally regulate and alleviate inflammatory diseases. We evaluated the therapeutic effect of OP9 cells in the mouse model of inflammatory bowel disease and found OP9 cells were able to ameliorate inflammatory bowel disease. We explored the existence of NLRP3 inflammasome in OP9 cells, and showed better therapeutic effects when the NLRP3 inflammasome was suppressed. Thus, OP9 cell line is similar to MSCs in characteristic and function, and is an ideal substitute for MSCs research. The preliminary exploration of the inflammasome system in OP9 cells lays a theoretical and methodological foundation for further study of MSCs.

References

Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N . Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019; 76(17):3323-3348. PMC: 11105258. DOI: 10.1007/s00018-019-03125-1. View

Do P, Wu C, Chiang Y, Hu C, Chen K . Mesenchymal Stem/Stromal Cell Therapy in Blood-Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects. Int J Mol Sci. 2021; 22(18). PMC: 8468469. DOI: 10.3390/ijms221810045. View

Lin Q, Li S, Jiang N, Jin H, Shao X, Zhu X . Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy. Autophagy. 2020; 17(10):2975-2990. PMC: 8525960. DOI: 10.1080/15548627.2020.1848971. View

Jiao J, Zhao G, Wang Y, Ren P, Wu M . MCC950, a Selective Inhibitor of NLRP3 Inflammasome, Reduces the Inflammatory Response and Improves Neurological Outcomes in Mice Model of Spinal Cord Injury. Front Mol Biosci. 2020; 7:37. PMC: 7062868. DOI: 10.3389/fmolb.2020.00037. View

Gu Y, Li T, Ding Y, Sun L, Tu T, Zhu W . Changes in mesenchymal stem cells following long-term culture in vitro. Mol Med Rep. 2016; 13(6):5207-15. DOI: 10.3892/mmr.2016.5169. View

Nakano T, Kodama H, Honjo T . Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science. 1994; 265(5175):1098-101. DOI: 10.1126/science.8066449. View

Naji A, Rouas-Freiss N, Durrbach A, Carosella E, Sensebe L, Deschaseaux F . Concise review: combining human leukocyte antigen G and mesenchymal stem cells for immunosuppressant biotherapy. Stem Cells. 2013; 31(11):2296-303. DOI: 10.1002/stem.1494. View

Yun C, Lee S . Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease. Int J Mol Sci. 2019; 20(7). PMC: 6479813. DOI: 10.3390/ijms20071619. View

Parekkadan B, Milwid J . Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010; 12:87-117. PMC: 3759519. DOI: 10.1146/annurev-bioeng-070909-105309. View

10.

Galipeau J, Sensebe L . Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018; 22(6):824-833. PMC: 6434696. DOI: 10.1016/j.stem.2018.05.004. View

11.

Holan V, Palacka K, Hermankova B . Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials. Cells. 2021; 10(3). PMC: 8001847. DOI: 10.3390/cells10030588. View

12.

Mridha A, Wree A, Robertson A, Yeh M, Johnson C, Van Rooyen D . NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J Hepatol. 2017; 66(5):1037-1046. PMC: 6536116. DOI: 10.1016/j.jhep.2017.01.022. View

13.

Harrell C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V . Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases. Cells. 2019; 8(12). PMC: 6952783. DOI: 10.3390/cells8121605. View

14.

Chen Y, Qin X, An Q, Yi J, Feng F, Yin D . Mesenchymal Stromal Cells Directly Promote Inflammation by Canonical NLRP3 and Non-canonical Caspase-11 Inflammasomes. EBioMedicine. 2018; 32:31-42. PMC: 6020748. DOI: 10.1016/j.ebiom.2018.05.023. View

15.

Hou B, Zhang Y, Liang P, He Y, Peng B, Liu W . Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype. Cell Death Dis. 2020; 11(5):377. PMC: 7229224. DOI: 10.1038/s41419-020-2565-2. View

16.

Zhang J, Chen Y, Yin D, Feng F, An Q, Liu Z . Caspase-3/NLRP3 signaling in the mesenchymal stromal niche regulates myeloid-biased hematopoiesis. Stem Cell Res Ther. 2021; 12(1):579. PMC: 8605603. DOI: 10.1186/s13287-021-02640-y. View

17.

Arend W, Palmer G, Gabay C . IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008; 223:20-38. DOI: 10.1111/j.1600-065X.2008.00624.x. View

18.

Cruz F, Rocco P . The potential of mesenchymal stem cell therapy for chronic lung disease. Expert Rev Respir Med. 2019; 14(1):31-39. DOI: 10.1080/17476348.2020.1679628. View

19.

Huang S, Chen Z, Fan B, Chen Y, Zhou L, Jiang B . A selective NLRP3 inflammasome inhibitor attenuates behavioral deficits and neuroinflammation in a mouse model of Parkinson's disease. J Neuroimmunol. 2021; 354:577543. DOI: 10.1016/j.jneuroim.2021.577543. View

20.

Liu Y, Tang B, Wang F, Tang L, Lei Y, Luo Y . Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner. Theranostics. 2020; 10(12):5225-5241. PMC: 7196297. DOI: 10.7150/thno.43716. View