The effects of serum separated from patients with sepsis on the expression of CXCR7 in mesenchymal stem cells (MSCs)
Archives of Advances in Biosciences,
Vol. 16 No. 1 (2025),
2 March 2025
,
Page 1-10
https://doi.org/10.22037/aab.v16i1.49304
Abstract
Introduction: Sepsis is a leading cause of death in intensive care unit (ICU) patients. This condition, in its advanced stage, leads to dysfunction of vital organs, resulting in the death of patients. Mesenchymal stem cells (MSCs) aid tissue regeneration by migrating to damaged areas, a process regulated by the CXCR7 gene. This study investigates the effect of serum from septic patients on the CXCR7 expression in MSCs.
Materials and Methods: The blood serum of 20 patients with sepsis was collected. The hUCB-MSCs were cultured under laboratory conditions (in vitro). Four groups of cells were treated with serum from patients and a control group was treated with serum from healthy volunteers. After 24 and 48 hours, the cells were trypsinized and RNA was extracted. cDNA was synthesized using a reverse transcription reaction and a specific kit. The expression level of this gene was determined using qRT-PCR.
Results: The results indicated that the expression of the CXCR7 gene in hUCB-MSCs treated with serum from sepsis patients significantly increased after 24 hours compared to the control group. Additionally, the expression level of this gene in the 48-hour treatment group showed a significant increase compared to the control groups and the 24-hour treatment group.
Conclusion: Exposure of hUCB-MSCs to septic patient serum led to a significant upregulation of CXCR7 compared with healthy serum (mean relative 2^−ΔΔCt fold-change: 24 h = 3.3-fold; 48 h = 19.3-fold; P < 0.01). These results are preliminary and warrant further functional and in vivo studies to confirm the biological and therapeutic implications of CXCR7 modulation in MSCs.
- Sepsis
- CXCR7 gene
- stem cells
- mesenchymal stem cells (MSCs)
- umbilical cord
- human
How to Cite
References
1] Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama. 2016 Feb 23;315(8):801-10. [PMID]
[2] Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Critical care. 2010 Feb 9;14(1):R15. [PMID]
[3] S Harrell CR, Sadikot R, Pascual J, Fellabaum C, Jankovic MG, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Mesenchymal stem cell‐based therapy of inflammatory lung diseases: current understanding and future perspectives. Stem cells international. 2019;2019(1):4236973. [PMID]
[4] Lalu MM, McIntyre L, Pugliese C, Stewart DJ. Safety of cell therapy with mesenchymal stromal cells (MSCs): a systematic review. D49. CLINICAL TRIALS IN CRITICAL CARE. 2010 May:A6043-. [PMID]
[5] McIntyre LA, Stewart DJ, Mei SH, Courtman D, Watpool I, Granton J, Marshall J, Dos Santos C, Walley KR, Winston BW, Schlosser K. Cellular immunotherapy for septic shock. A phase I clinical trial. American journal of respiratory and critical care medicine. 2018 Feb 1;197(3):337-47. [PMID]
[6] Sun XY, Ding XF, Liang HY, Zhang XJ, Liu SH, Duan XG, Sun TW. Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies. Stem cell research & therapy. 2020 Jun 3;11(1):214.[PMID]
[7] Lombardo E, van der Poll T, DelaRosa O, Dalemans W. Mesenchymal stem cells as a therapeutic tool to treat sepsis. World journal of stem cells. 2015 Mar 26;7(2):368. [PMID]
[8] S Vagima Y, Lapid K, Kollet O, Goichberg P, Alon R, Lapidot T. Pathways implicated in stem cell migration: the SDF-1/CXCR4 axis. InStem Cell Migration: Methods And Protocols 2011 May 4 (pp. 277-289). Totowa, NJ: Humana Press.[PMID]
[9] Ling L, Hou J, Liu D, Tang D, Zhang Y, Zeng Q, Pan H, Fan L. Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI). Stem cell research & therapy. 2022 Feb 23;13(1):79. [PMID]
[10] Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. Journal of Biological Chemistry. 2005 Oct 21;280(42):35760-6. [PMID]
[11] Heinrich EL, Lee W, Lu J, Lowy AM, Kim J. Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells. Journal of translational medicine. 2012 Apr 2;10(1):68.[PMID]
[12] Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ. β-arrestin-but not G protein-mediated signaling by the “decoy” receptor CXCR7. Proceedings of the National Academy of Sciences. 2010 Jan 12;107(2):628-32. [PMID]
[13] Singh AK, Arya RK, Trivedi AK, Sanyal S, Baral R, Dormond O, Briscoe DM, Datta D. Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12. Cytokine & growth factor reviews. 2013 Feb 1;24(1):41-9.[PMID]
[14] Wei ST, Huang YC, Chiang JY, Lin CC, Lin YJ, Shyu WC, Chen HC, Hsieh CH. Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation. Stem Cell Research & Therapy. 2021 May 29;12(1):314.[PMID]
[15] Xu J, Miao S, Wu T, Hu C, Huang D, Zhang X. CXCR7 promotes pulmonary vascular remodeling via targeting p38/MMP2 pathway in pulmonary arterial hypertension. Journal of Thoracic Disease. 2024 Apr 29;16(4):2460. [PMID]
[16] Zhang S, Yue J, Ge Z, Xie Y, Zhang M, Jiang L. Activation of CXCR7 alleviates cardiac insufficiency after myocardial infarction by promoting angiogenesis and reducing apoptosis. Biomedicine & Pharmacotherapy. 2020 Jul 1;127:110168. [PMID]
[17] Hao H, Hu S, Chen H, Bu D, Zhu L, Xu C, Chu F, Huo X, Tang Y, Sun X, Ding BS. Loss of endothelial CXCR7 impairs vascular homeostasis and cardiac remodeling after myocardial infarction: implications for cardiovascular drug discovery. Circulation. 2017 Mar 28;135(13):1253-64. [PMID]
[18] Liu S, Jia X, Li C, Han X, Yan W, Xing Y. CXCR7 silencing attenuates cell adaptive response to stromal cell derived factor 1α after hypoxia. PLoS One. 2013 Jan 31;8(1):e55290.[PMID]
[19] Pouzol L, Sassi A, Baumlin N, Tunis M, Strasser DS, Lehembre F, Martinic MM. CXCR7 antagonism reduces acute lung injury pathogenesis. Frontiers in Pharmacology. 2021 Nov 5;12:748740. [PMID]
[20] Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Communication and Signaling. 2011 May 14;9(1):12.[PMID]
[21] Jones GE, editor. Human cell culture protocols. Totowa, NJ: Humana Press; 1996 Apr 18. [LINK]
[22] Lukeš J. 1, 2, 4 1 Institute of Parasitology, Biology Centre, Czech Academy of Sciences, 37005 České Budějovice, Czech Republic; email:[email protected],[email protected] 2 Faculty of Science, University of South Bohemia, 37005 České Budějovice, Czech Republic 3 Institute of Microbiology. Czech Academy of Sciences.;379(81):129-44.[LINK]
[23] Otu A, Elston J, Nsutebu E. Sepsis in Africa: practical steps to stem the tide. Pan African Medical Journal. 2015;21(1). [PMID]
[24] Hou X, Zhang X, Zhao W, Zeng C, Deng B, McComb DW, Du S, Zhang C, Li W, Dong Y. Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nature nanotechnology. 2020 Jan 2;15(1):41-6.[PMID]
[25] Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017 Dec 14;9(6):7204. [PMID]
[26] Tang X, Li X, Li Z, Liu Y, Yao L, Song S, Yang H, Li C. Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells. Tumor Biology. 2016 Oct;37(10):13425-33. [PMID]
[27] Gonzalez MA, Ochoa CD. Multiorgan system failure in sepsis. InSepsis 2017 Aug 3 (pp. 67-71). New York, NY: Springer New York.[LINK]
[28] Warttig S, Alderson P, Evans DJ, Lewis SR, Kourbeti IS, Smith AF. Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients. Cochrane Database of Systematic Reviews. 2018(6). [PMID]
[29] Galstyan G, Makarova P, Parovichnikova E, Kuzmina L, Troitskaya V, Ghemdzhian E. The results of the single center pilot randomized Russian clinical trial of mesenchymal stromal cells in severe neutropenic patients with septic shock (RUMCESS). Int J Blood Res Disord. 2018;5(1):33. [LINK]
[30] J Jain K, Mohan KV, Roy G, Sinha P, Jayaraman V, Kiran, Yadav AS, Phasalkar A, Deepanshu, Pokhrel A, Perumal N. Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis. Scientific Reports. 2023 Sep 11;13(1):14977.[PMID]
- Abstract Viewed: 156 times
- PDF Downloaded: 59 times