• editor@ijmra.in
  • ISSN[Online] : 2643-9875  ||  ISSN[Print] : 2643-9840

Volume 06 Issue 10 October 2023

The Effect of Topical Gel Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) on TGF-Β and IL-6 Gene Expression in Wistar Rats Excision Wound Models
1Metalia, 2Chodidjah, 3Hadi Sarosa
1Postgraduate student of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
2,3Department of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
DOI : https://doi.org/10.47191/ijmra/v6-i10-23

Google Scholar Download Pdf
ABSTRACT:

Wounds on the skin result in damage to the epithelial tissue and skin structure, hampering wound healing and causing acute wounds to become chronic. Secretome Hypoxia Mesenchymal Stem Cells are capable of secretes cytokines and growth factors, including TGF-β which are useful for wound healing. IL-6 is a pro-inflammatory cytokine that is produced in infectious lesions and is also important in wound closure. The aim of the research was to prove the effect of topical SH-MSCs gel on TGF-β and IL-6 gene expression in male Wistar rats with an excision wound model. This study aims to prove the effect of topical gel administration secretome Hypoxia Mesenchymal Stem Cell (SH-MSCs) on TGF-β and IL-6 gene expression in male Wistar rats with an excision wound model. This study is Experimental research with Post-test Only Control Group Design. The number of samples was 18 male Wistar rats with the excision wound model divided into three groups, Group I (K-) was given a basic gel placebo, Group 2 (K+) was given a Clobetasol dose of 0.25g/kg, and Group 3 (P1) was given SH-MSCs gel at a dose of 400 μl/kg BW, treatment for 5 days, on day 6 the skin tissue was examined by RT-PCR to see the expression of the TGF-β and IL-6 genes analyzed by One Way Anova test, continued by Post Hoc LSD test. The average TGF-β gene expression in the P1 group was the highest (1.38) and the mean IL-6 gene expression in the P1 group was the lowest (0.72). One Way Anova test result showed a significant difference in TGF-β gene expression with a value of p=0.056 (p<0.05) and IL-6 p=0.47 (p<0.05). Post Hoc LSD test result on TGF-β gene expression shows that administration of 400μl/kg BW SH-MSCs can increase TGF-β gene expression and reduce IL-6 expression in Wistar rats with an excision wound model. The administration of topical gel SH-MSCs dose of 400 μl/kg BW was proven to significantly increase TGF-β levels in male Wistar rat excision wound model. The administration of topical SH MSCs dose of 400 μl/kg BW can reduce IL-6 levels in male Wistar rat excision wound models.

KEYWORDS:

SH-MSCs, hypoxia, TGF-β, IL-6, excision wounds

REFERENCES
1) Prastika DD, Setiawan B, Saputro AL, Yudaniayanti IS, Wibawati PA, Fikri F. Effect of topical shrimp chitosan on collagen density in healing excision wounds in white rats.Journal of Veterinary Medicine. 2020;3(1):101. doi:10.20473/jmv.vol3.iss1.2020.101-107

2) Aydemir I, Öztürk Ş, Kılıçaslan Sönmez P, Tuğlu Mİ. Mesenchymal stem cells in skin wound healing.Anatomy. 2016;10(3):228-234. doi:10.2399/ana.16.043

3) 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

4) Behm B, Babilas P, Landthaler M, Schreml S. Cytokines, chemokines and growth factors in wound healing. Journal of the European Academy of Dermatology and Venereology. 2012;26(7):812-820. doi:10.1111/j.1468-3083.2011.04415.x

5) 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

6) Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485-517. doi:10.1146/annurev.immunol.021908.132710

7) Daneshmandi L, Shah S, Jafari T, et al. Emergence of the Stem Cell Secretome in Regenerative Engineering. Trends Biotechnol. 2020;38(12):1373-1384. doi:10.1016/j.tibtech.2020.04.013

8) 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

9) Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: Pathophysiology and current methods for drug delivery, part 1: Normal and chronic wounds: Biology, causes, and approaches to care. Adv Skin Wound Care. 2012;25(7):304-314. doi:10.1097/01.ASW.0000416006.55218.d0

10) Pakaya D. The role of Vitamin C on the skin. Medika Tadulako: Medical Scientific Journal, Faculty of Medicine and Health Sciences. Published online 2014.

11) Desai S, Jagtap J, Sainani S, Bhonde R. Guiding stem cells for cutaneous repair.Current Research in Pharmacology and Drug Discovery. 2023;4. doi:10.1016/j.crphar.2022.100145

12) Murphy PS, Evans GRD. Advances in Wound Healing: A Review of Current Wound Healing Products. Plast Surg Int. 2012;2012:1-8. doi:10.1155/2012/190436

13) Rangatchew F, Vester-Glowinski P, Rasmussen BS, et al. Mesenchymal stem cell therapy of acute thermal burns: A systematic review of the effect on inflammation and wound healing. Burns. 2021;47(2):270-294. doi:10.1016/j.burns.2020.04.012

14) Chen D, Hao H, Fu X, Han W. Insight into reepithelialization: How do mesenchymal stem cells perform? Stem Cells Int. 2016;2016. doi:10.1155/2016/6120173

15) Jeschke MG, Rehou S, McCann MR, Shahrokhi S. Allogeneic mesenchymal stem cells for treatment of severe burn injury. Stem Cell Res Ther. 2019;10(1). doi:10.1186/s13287-019-1465-9

16) Lotfinia M, Lak S, Ghahhari NM, et al. FULL LENGTH Iranian Hypoxia Pre-Conditioned Embryonic Mesenchymal Stem Cell Secretome Reduces IL-10 Production by Peripheral Blood Mononuclear Cells. Biomed J. 2017;21(1):24-31. doi:10.6091/.21.1.24

17) Trisnadi S, Muhar AM, Putra A, Kustiyah AR. Hypoxia-preconditioned mesenchymal stem cells attenuate peritoneal adhesion through TGF-β inhibition. Universal Medicine. 2020;39(2):97-104. doi:10.18051/univmed.2020.v39.97-104

18) Behm B, Babilas P, Landthaler M, Schreml S. Cytokines, chemokines and growth factors in wound healing. Journal of the European Academy of Dermatology and Venereology. 2012;26(7):812-820. doi:10.1111/j.1468-3083.2011.04415.x

19) Gilbert RWD, Vickaryous MK, Viloria-Petit AM. Signalling by transforming growth factor beta isoforms in wound healing and tissue regeneration. J Dev Biol. 2016;4(2). doi:10.3390/jdb4020021

20) Su VYF, Lin CS, Hung SC, Yang KY. Mesenchymal stem cell-conditioned medium induces neutrophil apoptosis associated with inhibition of the NF-κb pathway in endotoxin- induced acute lung injury. Int J Mol Sci. 2019;20(9). doi:10.3390/ijms20092208

21) Su CM, Wang L, Yoo D. Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-92941-2

22) Bashir MM, Sharma MR, Werth VP. UVB and proinflammatory cytokines synergistically activate TNF-α production in keratinocytes through enhanced gene transcription. Journal of Investigative Dermatology. 2009;129(4):994-1001. doi:10.1038/jid.2008.332

23) Ayu K, Erika A, Mas A, Batari UA, Watampone T.The Effect of Applying Topical Red Dragon Fruit Extract Cream (Hylocereus Polyrhizuz) to Acute Wounds on Interleukin-6 Levels in the Inflammatory Phase in Wistar.; 2018. https://www.researchgate.net/publication/323545270

24) 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

25) Jeschke MG, Rehou S, McCann MR, Shahrokhi S. Allogeneic mesenchymal stem cells for treatment of severe burn injury. Stem Cell Res Ther. 2019;10(1). doi:10.1186/s13287-019-1465-9

26) Priyandari Y, Arfina Titi Maulidah Umatjina S.Topical Jatropha Curcas Sap Accelerates the Healing Time of Excision Wounds in Mice (Effect of Jatropha Curcas Topical Increases Wound Healing Excision Period of Mice).

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) Gurtner G, Wong VW. Wound healing: normal and abnormal. Grabb and Smith’s plastic surgery. 2007;6:15-22.

29) 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

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) Widyaningsih W.Effect of Hypoxic Mesenchymal Stem Cell Secretome Administration on C-Peptide, IL-6 Levels, and Type-2 Macrophage Polarization (In Vivo Experimental Study in Type 2 Diabetes Mellitus Obese Rats) (Doctoral Dissertation, Sultan Agung Islamic University (Indonesia)).; 2022.

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) 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

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) Muhar 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

36) Pan XH, Huang X, Ruan GP, et al. Umbilical cord mesenchymal stem cells are able to undergo differentiation into functional islet-like cells in type 2 diabetic tree shrews. Mol Cell Probes. 2017;34:1-12. doi:10.1016/j.mcp.2017.04.002
Volume 06 Issue 10 October 2023

There is an Open Access article, distributed under the term of the Creative Commons Attribution – Non Commercial 4.0 International (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits remixing, adapting and building upon the work for non-commercial use, provided the original work is properly cited.


Our Services and Policies

Authors should prepare their manuscripts according to the instructions given in the authors' guidelines. Manuscripts which do not conform to the format and style of the Journal may be returned to the authors for revision or rejected.

The Journal reserves the right to make any further formal changes and language corrections necessary in a manuscript accepted for publication so that it conforms to the formatting requirements of the Journal.

International Journal of Multidisciplinary Research and Analysis will publish 12 monthly online issues per year,IJMRA publishes articles as soon as the final copy-edited version is approved. IJMRA publishes articles and review papers of all subjects area.

Open access is a mechanism by which research outputs are distributed online, Hybrid open access journals, contain a mixture of open access articles and closed access articles.

International Journal of Multidisciplinary Research and Analysis initiate a call for research paper for Volume 07 Issue 12 (December 2024).

PUBLICATION DATES:
1) Last Date of Submission : 26 December 2024 .
2) Article published within a week.
3) Submit Article : editor@ijmra.in or Online

Why with us

International Journal of Multidisciplinary Research and Analysis is better then other journals because:-
1 : IJMRA only accepts original and high quality research and technical papers.
2 : Paper will publish immediately in current issue after registration.
3 : Authors can download their full papers at any time with digital certificate.

The Editors reserve the right to reject papers without sending them out for review.

Authors should prepare their manuscripts according to the instructions given in the authors' guidelines. Manuscripts which do not conform to the format and style of the Journal may be returned to the authors for revision or rejected. The Journal reserves the right to make any further formal changes and language corrections necessary in a manuscript accepted for publication so that it conforms to the formatting requirements of the Journal.

Indexed In
Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar Avatar