Aim Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation of the pancreatic islets of Langerhans. Hyperglycaemia leads to suppressed antioxidant enzyme and increased inflammation in the pancreatic cell, resulting in pancreatic cell death. Hypoxic secretome mesenchymal stem cells (HS-MSCs) are soluble molecules secreted by MSCS that have the antiinflammation ability by secreting various cytokines including IL-10 and TGF-β which potent as a promising therapeutic modality for T1DM. This study aims to investigate the role of HS-MSCs in regulating superoxide dismutase (SOD) and caspase-3 gene expression in T1DM model. Methods Twenty male Wistar rats (6 to 8 weeks old) were randomly divided into four groups (sham, control, HS-MSCs 0.5 mL and HS-MSCs 1 mL intraperitoneal treatment group). Streptozotocin (STZ) 60mg/kgBB was conducted once on day 1, HS-MSCs 0.5mL (T1) and HS-MSCs 1 mL (T2) were administrated intraperitoneally on day 7, 14, and 21 after STZ administration. The rats were sacrificed on day 28; the gene expression of SOD and IL-6 was analysed by qRT-PCR. Results This study showed that the ratio of SOD significantly increased in HS-MSCs treatment associated with suppression of IL-6 gene expression. Conclusion HS-MSCs administration suppresses oxidative stress and inflammation by up regulating SOD and inhibiting IL-6 to control T1DM.
Ma Q. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401–26.
2.
Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α-smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci. 2021;9:35–41.
3.
Darlan DM, Munir D, Putra A, Alif I, Amalina ND, Jusuf NK, et al. Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients.
4.
D MD, D M, N KJ, A P, R I, I A. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica. 2020;17:408–13.
5.
Drawina P, Putra A, Nasihun T, Prajoko YW, Dirja BT, Amalina ND. Increased serial levels of platelet‐ derived growth factor using hypoxic mesenchymal stem cell‐conditioned medium to promote closure acceler‐ation in a full‐thickness wound. Indonesian J Biotech. 2022;27:36–42.
6.
Muhar AM, Mukharim F, Hermansyah D, Putra A, Hidayah N, Amalina ND, et al. Hypoxic mesenchymal stem cell‐conditioned medium accelerates wound healing by regulating IL‐10 and TGF‐β levels in a full‐thickness‐wound rat model. Indonesian J Biotechnol. 2022;27:187–94.
7.
Restimulia L, Ilyas S, Munir D, Madiadipoera T, Farhat F, Sembiring RJ, et al. Rats’ umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats.
8.
Nederstigt C, Uitbeijerse BS, Janssen LGM, Corssmit EPM, Koning EJP, Dekkers OM. Associated autoimmune disease in type 1 diabetes patients: a systematic review and meta-analysis. Eur J Endocrinol. 2019;180:135–44.
9.
Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol. 2020;11(1582).
10.
Madi M, Babu S, Kumari S, Shetty S, Achalli S, Madiyal A, et al. Status of serum and salivary levels of superoxide dismutase in type 2 diabetes mellitus with oral manifestations: a case control study. Ethiop J Health Sci. 2016;26:523–32.
11.
Cui T, Lai Y, Janicki JS, Wang X. Nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated protein quality control in cardiomyocytes. Front Biosci (Landmark Ed. 2016;21(192).
12.
Barry JC, Shakibakho S, Durrer C, Simtchouk S, Jawanda KK, Cheung ST, et al. Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes. Sci Rep. 2016;6:1–9.
13.
Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2017;1863:585–97.
14.
Restimulia L, Ilyas S, Munir D, Putra A, Madiadipoera T, Farhat F, et al. The CD4+ CD25+ FoxP3+ regulatory T cells regulated by MscS suppress plasma cells in a mouse model of allergic rhinitis. Med Arch. 2021;75(256).
15.
Serafini MM, Catanzaro M, Fagiani F, Simoni E, Caporaso R, Dacrema M, et al. Modulation of Keap1/Nrf2/ ARE signaling pathway by curcuma- and garlic-derived hybrids. Front Pharmacol. 2020;10(1597).
16.
Angeloni C, Gatti M, Prata C, Hrelia S, Maraldi T. Role of mesenchymal stem cells in counteracting oxidative stress—related neurodegeneration. Int J Mol Sci. 2020;21:1–28.
17.
Penta A, B M, S R, B FD, M V, O E, et al. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation. PLoS One. 2013;8(54722).
18.
Schmidt-Arras D, Rose-John S. Endosomes as Signaling Platforms for IL-6 Family Cytokine Receptors. Frontiers in Cell and Develop Biol. 2021;9:688314.
19.
Huang J, Tan Q, Tai N, Pearson JA, Li Y, Chao C, et al. IL-10 deficiency accelerates type 1 diabetes development via modulation of innate and adaptive immune cells and gut microbiota in BDC2.5 NOD Mice. Front Immunol. 2021;12:1–13.
20.
Dias I, Pinheiro D, Silva KR, Stumbo AC, Thole A, Cortez E, et al. Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes. Current Res Pharmacol Drug Discov. 2021;2(100069).
21.
Ribot J, Caliaperoumal G, Paquet J, Boisson-vidal C, Petite H, Anagnostou F. Type 2 diabetes alters mesenchymal stem cell secretome composition and angiogenic properties. J Cell Mol Med. 2017;21:349–63.
22.
Gomes KB. IL-6 and type 1 diabetes mellitus: T cell responses and increase in IL-6 receptor surface expression. Ann Transl Med. 2017;5:16–8.
23.
Ferreira-Hermosillo A, Molina-Ayala M, RamírezRentería C, Vargas G, Gonzalez B, Isibasi A, et al. Inflammatory cytokine profile associated with metabolic syndrome in adult patients with type 1 diabetes. J Diabetes Res. 2015;
24.
Ngaski A. Correlation of antioxidants enzymes activity with fasting blood glucose in diabetic patients in Sokoto, Nigeria. J Adv Med Med Res. 2018;25:1–6.
25.
Roep BO, Thomaidou S, Tienhoven R, Zaldumbide A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system? Nat Rev Endocrinol. 2021;17:150–61.
26.
Aouacheri O, Saka S, Krim M, Messaadia A, Maidi I. The Investigation of the oxidative stress-related parameters in type2 diabetes mellitus. Can J Diabete. 2015;39:44–9.
27.
O NB, H B, K E amadi, F E, N N. Superoxide dismutase and glutathione peroxidase levels in patients with long standing type 2 diabetes in Port Harcourt, Rivers State, Nigeria. International Journal of Science and Research (IJSR. 2016;5:1282–8.
28.
Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta Gen Subj. 2014;1840:2709–29.
29.
Padgett LE, Broniowska KA, Hansen PA, Corbett JA, Tse HM. The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis. Ann N Y Acad Sci. 2013;1281:16–35.
30.
Dogan Y, Akarsu S, Ustundag B, Yilmaz E, IL-1β GMKS. IL-2, and IL-6 in insulin-dependent diabetic children. Mediators Inflamm. 2006;2006(59206).
31.
Chen J, Stimpson SE, Fernandez-Bueno GA, Mathews CE. Mitochondrial reactive oxygen species and type 1 diabetes. Antioxid Redox Signal. 2018;29:1361–72.
32.
Piganelli JD, Delmastro MM. Oxidative stress and redox modulation potential in type 1 diabetes. Clin Dev Immunol. 2011;2011(593863).
33.
Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R. Increased blood levels of growth factors, proinflammatory cytokines, and Th17 cytokines in patients with newly diagnosed type 1 diabetes. PLoS One. 2015;10:1–16.
34.
Buzzetti R, Tuomi T, Mauricio D, Pietropaolo M, Zhou Z, Pozzilli P, et al. Management of latent autoimmune diabetes in adults: a consensus statement from an international expert panel. Diabetes. 2020;69:2037–47.
35.
Dong S, Lau H, Chavarria C, Alexander M, Cimler A, Elliott JP, et al. Effects of Periodic Intensive Insulin Therapy. An Updated Review Current Therapeutic Res. 2019;90:61–7.
36.
D MD, D M, N KJ, A P, R I, I A. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica. 2020;17:408–13.
37.
Putra A, Ridwan FB, Putridewi AI, Kustiyah AR, Wirastuti K, Sadyah NA, et al. The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci. 2018;6:1779–83.
38.
Darlan DM, Munir D, Putra A, Jusuf NK. MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC. J Formosan Med Assoc. 2021;120:602–8.
39.
Sungkar T, Putra A, Lindarto D, Sembiring RJ. Intravenous umbilical cord-derived mesenchymal stem cells transplantation regulates hyaluronic acid and interleukin-10 secretion producing low-grade liver fibrosis in experimental rat. Med Arch. 2020;74:177–82.
40.
Pankajakshan D, Agrawal DK. Mesenchymal stem cell paracrine factors in vascular repair and regeneration. J Biomed Technol Res. 2014;1:1–21.
41.
Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(2062).
42.
Katuchova J, Harvanova D, Spakova T, Kalanin R, Farkas D, Durny P, et al. Mesenchymal stem cells in the treatment of type 1 diabetes mellitus. Endocr Pathol. 2015;26:95–103.
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