1Dessy Tri Natalia, 2Prasetyowati Subchan, 3Adi Muradi Muhar
1Postgraduate student of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
2 Department of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
3Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
DOI : https://doi.org/10.47191/ijmra/v6-i10-28Google Scholar Download Pdf
ABSTRACT:
Wounds are damage to normal anatomical structures and functions due to pathological processes that originate internally or externally and affect certain organs. The wound healing process consists of four highly integrated and overlapping hemostasis phases, inflammation, proliferation, and remodeling or network resolution. Therapy using Mesenchymal Stem Cells (MSC) is considered effective in improving skin wound healing because it has the potential for differentiation and immunoregulation and there is no potential for post-treatment rejection. This research aims to prove the influence of secretome hypoxia mesenchymal stem cells (SH-MSC) on PDGF and IF-Gamma gene expression in Wistar rats using the excision wound model. This research is in-vivo experimental research with Post-test Only Control Group Design. The research subjects were 18 male Wistar rats with excision wound models divided into three groups there are placebo gel (negative control), Clobetasol at a dose of 0.25g/kg (positive control), and the P1 group SH-MSC gel at a dose of 400 μl/kg BW, were given treatment for 5 days. On the 6th day, the skin tissue was examined using the RT-PCR method to see the expression of the PDGF and IF-gamma genes. Statistical analysis using One-way ANOVA and Post Hoc LSD test. The average PDGF gene expression in the P1 group was the highest, followed by the positive control. The lowest average expression of the PDGF gene was found in the negative control. The average IFN-γ gene expression in the negative control was the highest, followed by the positive control group. The lowest average expression of the IFN-γ gene was found in the P1 group. The administration of SH-MSCs topical gel 400μl/kg BW increased PDGF expression in male Wistar rats with excision wound models, whereas the administration of gel secretome SH-MSC at a dose of 400μl/kg BW can reduce IFN-γ levels in male Wistar rats with the excision wound model.
KEYWORD:SH-MSC, hypoxia, PDGF gene, IFN-γ gene, excision wound
REFERENCES1) Anas Y, Rositasati R, Fitriani MR, Suharjono. Development of Type 2 Diabetic Mellitus Rat Experimental Animal Model due to Insulin-Induced Resistance 1. Diane, et al. 2018. Development of Hypoxic Conditions for Gel Production from Conditioned Mesenchymal Stem Cell Medium from Fat Tissue As a Wound-Healing Topical Material for Diabetic Foot Ulcer (DFU) Patients. Published online 2018.
2) Lindholm C, Searle R. Wound management for the 21st century: combining effectiveness and efficiency. Int Wound J. 2016;13:5-15. doi:10.1111/iwj.12623
3) Purnama H, Ratnawulan S.Raya Bandung-Sumedang Km 21 Jatinangor 45363 Tel.
4) Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics. 2020;12(8):1-30. doi:10.3390/pharmaceutics12080735
5) Jeschke MG, Rehou S, McCann MR, Shahrokhi S. Allogeneic mesenchymal stem cells for the treatment of severe burn injury. Stem Cell Res Ther. 2019;10(1). doi:10.1186/s13287-019-1465-9
6) Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9). doi:10.3390/ijms18091852
7) Ryan. 2020. The Effect of Administration of Puncamesenchymal Cells on Expression of Vascular Cell Adhesion Molecule-1(VCAM-1) in Placental Mice inducing Prista Lupus Model.
8) Tran C, Damaser MS. Stem cells as drug delivery methods: Application of stem cell secretome for regeneration. Adv Drug Deliv Rev. 2015;82:1-11. doi:10.1016/j.addr.2014.10.007
9) Wiredu Ocansey DK, Pei B, Yan Y, et al. Improved therapeutics of modified mesenchymal stem cells: An update. J Transl Med. 2020;18(1). doi:10.1186/s12967-020-02234-x
10) Folestad E, Kunath A, Wågsäter D. PDGF-C and PDGF-D signaling in vascular diseases and animal models. Mol Aspects Med. 2018;62:1-11. doi:10.1016/j.mam.2018.01.005
11) Vaidyanathan L. Growth factors in wound healing ⇓ a review. Biomedical and Pharmacology Journal. 2021;14(3):1469-1480. doi:10.13005/bpj/2249
12) Health J, Verdiana R, Ali H, Kadri H.Expression of PDGF-B and SCUBE 1 in Carotid Arteries of Ligated and Unligated Mice. Vol 4.; 2015. http://jurnal.
13) Pdgf E, Epidermis DK, Healing P, Radiation D, Sprague-Dawley T.Effect of Topical Administration of Ozonized Aloe Vera Oil on the Effects of Ozonated Aloe Vera Oil Topical on the PDGF Expression and Epidermal Thickness in Radiation Dermatitis in Sprague Dawley.
14) Kang YM, Hong CH, Kang SH, et al. Anti-photoaging effect of plant extract fermented with Lactobacillus buchneri on CCD-986sk fibroblasts and HaCaT keratinocytes. J Funct Biomater. 2020;11(1). doi:10.3390/jfb11010003
15) Lee LY, Liu SX. Pathogenesis of Photoaging in Human Dermal Fibroblasts. Int J Dermatol Venereol. Published online 2021:37-42. doi:10.1097/JD9.0000000000000068
16) Putra A, Ridwan FB, Putridewi AI, 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(10):1779-1783. doi:10.3889/oamjms.2018.404
17) MacLeod AS, Mansbridge JN. The Innate Immune System in Acute and Chronic Wounds. Adv Wound Care (New Rochelle). 2016;5(2):65-78. doi:10.1089/wound.2014.0608
18) Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol. 2018;9(MAY). doi:10.3389/fimmu.2018.00847
19) Drago D, Cossetti C, Iraci N, et al. The stem cell secretome and its role in brain repair. Biochemistry. 2013;95(12):2271-2285. doi:10.1016/j.biochi.2013.06.020
20) Madrigal M, Rao KS, Riordan NH. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med. 2014;12(1). doi:10.1186/s12967-014-0260-8
21) da Silva Meirelles L, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 2009;20(5-6):419-427. doi:10.1016/j.cytogfr.2009.10.002
22) Oh JY, Ko JH, Lee HJ, et al. Mesenchymal stem/stromal cells inhibit the NLRP3 Inflammasome by Decreasing Mitochondrial Reactive Oxygen Species. Stem Cells. 2014;32(6):1553-1563. doi:10.1002/stem.1608
23) Kuntardjo N, Dharmana E, Chodidjah C, Nasihun TR, Putra A. TNF-α-Activated MSC-CM Topical Gel Effective in Increasing PDGF Level, Fibroblast Density, and Wound Healing Process Compared to Subcutaneous Injection Combination. Bandung Medical Magazine. 2019;51(1):1-6. doi:10.15395/mkb.v51n1.1479
24) Ayu D, Istiqomah F, Djannah D, Mulyani SP.The Effect of Hypoxic Mesenchymal Stem Cells on The Gene Expression of Transforming Growth Factors-β in Wistar Rats Excision Wound Model. Vol 1.; 2022.
25) Bartaula-Brevik S. Secretome of Mesenchymal Stem Cells Grown in Hypoxia Accelerates Wound Healing and Vessel Formation In Vitro. Int J Stem Cell Res Ther. 2017;4(1). doi:10.23937/2469-570x/1410045
26) Priyandari Y, Arfina Titi Maulidah Umatjina S.Topical Jatropha Curcas (Effect of Jatropha Curcas) Increases Wound Healing Excision Period of Mice (Effect of Jatropha Curcas).
27) Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: Molecular and cellular mechanisms. Journal of Investigative Dermatology. 2007;127(3):514-525. doi:10.1038/sj.jid.5700701
28) Gushiken LFS, Beserra FP, Bastos JK, Jackson CJ, Pellizzon CH. Cutaneous wound healing: An update from physiopathology to current therapies. Life. 2021;11(7). doi:10.3390/life11070665
29) Xiao S, Huang G, Wei Z, et al. IL-10 Gene-modified human amniotic mesenchymal stem cells augment regenerative wound healing by multiple synergistic effects. Stem Cells Int. 2019;2019. doi:10.1155/2019/9158016
30) Yustianingsih V, Sumarawati T, Putra A. Hypoxia enhances self-renewal properties and markers of mesenchymal stem cells. Universal Medicine. 2019;38(3):164-171. doi:10.18051/univmed.2019.v38.164-171
31) Widowati W, Rihibiha DD, Khiong K, Widodo MA, Sumitro SB, Bachtiar I. Hypoxia in Mesenchymal Stem Cell. in:Hypoxia and Human Diseases. InTech; 2017. doi:10.5772/65510
32) Putra A, Alif I, Hamra N, et al.MSC-Released TGF-β Regulate α-SMA Expression of Myofibroblast during Wound Healing. Journal of Stem Cells & Regenerative Medicine.; 2020.
33) Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, LeRoux MA. Concise Review: Role of Mesenchymal Stem Cells in Wound Repair. Stem Cells Transl Med. 2012;1(2):142-149. doi:10.5966/sctm.2011-0018
34) Singampalli KL, Balaji S, Wang X, et al. The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing. Front Cell Dev Biol. 2020;8. doi:10.3389/fcell.2020.00636
35) Isakson M, De Blacam C, Whelan D, McArdle A, Clover AJP. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential. Stem Cells Int. 2015;2015. doi:10.1155/2015/831095
36) Kang SK, Shin IS, Ko MS, Jo JY, Ra JC. Journey of mesenchymal stem cells for homing: Strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int. Published online 2012. doi:10.1155/2012/342968
37) Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, LeRoux MA. Concise Review: Role of Mesenchymal Stem Cells in Wound Repair. Stem Cells Transl Med. 2012;1(2):142-149. doi:10.5966/sctm.2011-0018
38) aMuhar AM, Putra A, Warli SM, Munir D. Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Maced J Med Sci. 2019;7(23):3937-3943. doi:10.3889/oamjms.2019.713
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