Aim To investigate the role of hypoxia-preconditioned mesenchymal stem cells (H-MSCs) in preventing peritoneal adhesion by regulating IL-6 at days 6 and 12. Methods Twenty-four PAs rat model weighing 250 g to 300 g were randomly allocated into 4 groups: sham (Sh), control (C), H-MSCs treatment group at dose 1.5 x 106 (T1) and 3 x 106 (T2). To induce H-MSCs, all MSCs population were incubated under hypoxia state (5% O2), 5% CO2, and 37o C for 24 hours. Expression level of IL-6 was performed using ELISA. Morphological appearance of adhesion was observed by visualizing the existence of adhesion formation in intestinal. Results In this study we found that there was a trend of decrease of IL-6 level on day 6 following MSCs treatments. Interestingly, there was a significant decrease of IL-6 level on day 12 in all treatment groups. Also, no adhesion occurred in T2 group. Conclusions H-MSCs prevent PA development by suppressing the prolonged release of IL-6 at proliferation phase.
Capella-Monsonís H, Kearns S, Kelly J, Dimitrios. Battling adhesions: from understanding to prevention. BMC Biomed Eng. 2019;5.
2.
Broek T, Krielen R, P, Saverio D, S. Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. World J Emerg Surg. 2018;24.
3.
Thorbjörn S, Malin C, Urban K. Mechanisms of adhesive small bowel obstruction and outcome of surgery; a population-based study. BMC Surgery. 2020;62.
4.
Weisel J, Litvinov R. Fibrin formation, structure and properties. Subcell Biochem. 2017;405–56.
5.
Bester J, Pretorius E. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep. 2016;32188.
6.
Baker S, S. Review: A critical role for plasminogen in inflammation. J Exp Med. 2020;4.
7.
Xue X, Falcon D. The role of immune cells and cytokines in intestinal wound healing. Int J Mol Sci. 2019;6097.
8.
Li P, Gong Z, Shultz L, Ren G. Mesenchymal stem cells: from regeneration to cancer. Pharmacol Ther. 2019;42–54.
9.
Putra A, Pertiwi D, Milla M, Indrayani U, Jannah D, Sahariyani M, et al. Hypoxiapreconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced J Med Sci. 2019;305–10.
10.
Almeria C, Weiss R, Roy M, Tripisciano C, Kasper C, Egger W, et al. Hypoxia conditioned mesenchymal stem cell-derived extracellular vesicles induce increased vascular tube formation in vitro. Front Bioeng Biotechnol. 2019;292.
11.
Fábián Z. The Effects of hypoxia on the immunemodulatory properties of bone marrow-derived mesenchymal stromal cells. Stem Cells Int. 2019;2509606.
12.
Samsonraj R, Rai B, Sathiyanathan P, Puan K, Rötzschke O, Hui J, et al. Establishing criteria for human mesenchymal stem cell potency. Stem Cells. 2015;1878–91.
13.
Mutsaers S, Prêle C, Pengelly S, Herrick S. Mesothelial cells and peritoneal homeostasis. Fertil Steril. 2016;1018–24.
14.
Cronjé H, Nienaber-Rousseau C, Zandberg L, De Lange Z, Green F, Pieters M. Fibrinogen and clot-related phenotypes determined by fibrinogen polymorphisms: Independent and IL-6-interactive associations. PLoS One. 2017;11.
15.
Lin H, Xu L, Yu S. Therapeutics targeting the fibrinolytic system. Exp Mol Med. 2020;367–79.
16.
Dan Pengembangan. We would also like to thank the Stem Cell and Cancer Research Laboratory, Medical Faculty, Universitas Islam Sultan Agung Semarang for all facilities to finish this research. FUNDING DRPM contract. 2020;
17.
Zubaidi A, Hussain T, Alzoghaibi M. The time course of cytokine expressions plays a determining role in faster healing of intestinal and colonic anastomatic wounds. Saudi J Gastroenterol. 2015;412–7.
18.
Muhar A, Putra A, Warli S, Delfitri M. Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the IL-10 expression. Open Access Maced J Med Sci. 2019;3937–43.
19.
Kim Y. Comparative study for preventive effects of intra-abdominal adhesion using cyclo-oxygenase-2 enzyme (COX-2) inhibitor, low molecular weight heparin (LMWH), and synthetic barrier. Yonsei Med J. 2013;1491–7.
20.
Trisnadi S, Muhar A, Putra A, Kustiyah. AR. Hypoxia-preconditioned mesenchymal stem cells attenuate peritoneal adhesion through TGF-β inhibition. Univ Med. 2020;97–104.
21.
Ikhsan R, Putra A, Munir D, Darlan D, Suntoko B, Retno A. Mesenchymal stem cells induce regulatory T-cell population in human SLE. Bangladesh J Med Sci. 2020;743–8.
22.
Mutsaers S, Birnie K, Lansley S, Herrick S, Lim C, Prêle C. Mesothelial cells in tissue repair and fibrosis. Front Pharmacol. 2015;113.
23.
Capella-Monsonís H, Kearns S, Kelly J, Zeugolis D. Battling adhesions: from understanding to prevention. BMC Biomed Eng. 2019;5.
24.
Xu W, Xu R, Li Z, Wang Y, Hu R. Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1α signalling. J Cell Mol Med. 2019;(3):1899–907.
25.
Jafari-Sabet M, Shishegar A, Saeedi A, Ghahari S. Pentoxifylline Increases Antiadhesion Effect of Streptokinase on Postoperative Adhesion Formation: Involvement of Fibrinolytic Pathway. Indian J Surg. 2015;(Suppl 3):837–42.
26.
Rocca A, Aprea G, Surfaro G, Amato M, Giuliani A, Paccone M, et al. Prevention and treatment of peritoneal adhesions in patients affected by vascular diseases following surgery: a review of the literature. Open Med (Wars). 2016;106–14.
27.
Kuhn K, Manieri N, Liu T, Stappenbeck T. IL-6 stimulates intestinal epithelial proliferation and repair after injury. PLoS One. 2014;114195.
28.
West N. Coordination of immune-stroma crosstalk by il-6 family cytokines. Front Immunol. 2019;1093.
29.
Pankajakshan D, Agrawal D. Mesenchymal stem cell paracrine factors in vascular repair and regeneration. J Biomed Technol Res. 2014;1.
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