Perbandingan Pemberian Mesenchymal Stem Cell Hipoksia dan Normoksia Terhadap Ekspresi IL-10 pada Tikus Model Luka Eksisi
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Submitted
14 December 2021
Published
27 December 2021
Keywords:
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Mesenchymal Stem Cells, Hipoksia, IL-10, Luka Eksisi, qPCR
Abstract
Latar Belakang: Proses penyembuhan luka eksisi melibatkan rangkaian respons seluler yang kompleks untuk membalikkan pembentukan integritas jaringan kulit. Proses ini membutuhkan komunikasi parakrin yang melibatkan sitokin-sitokin antiinflamasi, terutama interleukin 10 (IL-10). Di sisi lain, sel punca mesenkimal prekondisi hipoksia (H-MSCs) dipercaya mampu meningkatkan sekresi IL-10 berkontribusi pada percepatan penyembuhan luka dibandingkan dengan sel punca mesenkimal prekondisi normoksia (N-MSCs). Tujuan: Penelitian ini bertujuan untuk membandingkan H-MSCs dan N-MSCs dalam meregulasi ekspresi serial IL-10 yang terkait dengan peningkatan kepadatan kolagen pada model hewan luka eksisi. Metode: Tiga puluh enam tikus Wistar jantan dengan luka eksisi dibuat sebagai model hewan dengan metode biopsi 6 mm. Hewan secara acak dibagi menjadi empat kelompok yang terdiri dari empat kelompok perlakuan: N-MSCs 1x106, H-MSCs 1x106, Kontrol (perlakuan PBS) dan Sham (tikus sehat yang tidak diobati). Pemberian perlakuan dilakukan 2 kali secara intra peritonial pada hari ke 0. Jaringan kulit dikoleksi pada hari ke 3, 6 dan 9 pasca injeksi. Ekspresi IL-10 diperiksa dengan qPCR. Hasil: Penelitian ini menunjukkan bahwa terjadi peningkatan IL-10 yang signifikan pada hari ke 3 dan 6 setelah perlakuan H-MSCs dan menurun pada hari ke-9 dibandingkan dengan perlakuan N-MSCs. Kesimpulan: H-MSCs dapat memperbaiki ekspresi serial IL-10 yang mengarah pada perbaikan luka model tikus luka eksisi dibandinglkan dengan N-MSCs.
References
Chen, D., Hao, H., Fu, X., & Han, W. (2016). Insight into reepithelialization: How do mesenchymal stem cells perform? Stem Cells International, 2016. https://doi.org/10.1155/2016/6120173
Consistently, A. V. (n.d.). Hypoxic Preconditioning of Mesenchymal Stromal Cells Induces Metabolic Changes , Enhances Survival , and Promotes Cell Retention In Vivo.
Gao, W., He, R., Ren, J., Zhang, W., Wang, K., Zhu, L., & Liang, T. (2021). Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway. FEBS Open Bio, 11(5), 1364–1373. https://doi.org/10.1002/2211-5463.13142
Han, C., Cheng, B., & Wu, P. (2020). Clinical guideline on topical growth factors for skin wounds. Burns & Trauma, 8. https://doi.org/10.1093/burnst/tkaa035
Ho, C. H., Lan, C. W., Liao, C. Y., Hung, S. C., Li, H. Y., & Sung, Y. J. (2018). Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model. Journal of the Chinese Medical Association, 81(3), 268–276. https://doi.org/10.1016/j.jcma.2017.03.013
Isakson, M., De Blacam, C., Whelan, D., McArdle, A., & Clover, A. J. P. (2015). Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential. Stem Cells International, 2015. https://doi.org/10.1155/2015/831095
King, A., Balaji, S., Le, L. D., & Crombleholme, T. M. (2014). Regenerative Wound Healing : The Role of Interleukin-10. 3(4), 315–323. https://doi.org/10.1089/wound.2013.0461
Li, Z., Wei, H., Deng, L., Cong, X., & Chen, X. (2010). Expression and secretion of interleukin-1β, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells. FEBS Journal, 277(18), 3688–3698. https://doi.org/10.1111/j.1742-4658.2010.07770.x
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25(4), 402–408. https://doi.org/10.1006/METH.2001.1262
Madrigal, M., Rao, K. S., & Riordan, N. H. (2014). A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. Journal of Translational Medicine, 12(1), 1–14. https://doi.org/10.1186/s12967-014-0260-8
Mazini, L., Rochette, L., Hamdan, Y., & Malka, G. (2021). Skin Immunomodulation during Regeneration: Emerging New Targets. Journal of Personalized Medicine 2021, Vol. 11, Page 85, 11(2), 85. https://doi.org/10.3390/JPM11020085
Motegi, S., & Ishikawa, O. (2016). Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. Journal of Dermatological Science. https://doi.org/10.1016/j.jdermsci.2016.11.005
Muhar, A. M., Putra, A., Warli, S. M., & Munir, D. (2019). Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Macedonian Journal of Medical Sciences. https://doi.org/10.3889/oamjms.2019.713
Nosenko, M. A., Ambaryan, S. G., & Drutskaya, M. S. (2019). Proinflammatory Cytokines and Skin Wound Healing in Mice. Molecular Biology, 53(5), 653–664. https://doi.org/10.1134/S0026893319050121
Numakura, S., Uozaki, H., Kikuchi, Y., Watabe, S., Togashi, A., & Watanabe, M. (2019). Mesenchymal stem cell marker expression in gastric cancer stroma. Anticancer Research, 39(1), 387–393. https://doi.org/10.21873/anticanres.13124
Oh, E. J., Lee, H. W., Kalimuthu, S., Kim, T. J., Kim, H. M., Baek, S. H., Zhu, L., Oh, J. M., Son, S. H., Chung, H. Y., & Ahn, B. C. (2018). In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model. Journal of Controlled Release, 279, 79–88. https://doi.org/10.1016/J.JCONREL.2018.04.020
Putra, A, Ridwan, F. B., Putridewi, A. I., Kustiyah, A. R., Wirastuti, K., Nac, S., & others. (2018). The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci, 610, 1779.
Putra, Agung. (2019). Hypoxia-preconditioned MSCs Have Superior Effect in Ameliorating Renal Function on Acute Renal Failure Animal Model. 1–6.
Sabry, D., Mohamed, A., Monir, M., & Ibrahim, H. A. (2019). The effect of mesenchymal stem cells derived microvesicles on the treatment of experimental CCL4 induced liver fibrosis in rats. International Journal of Stem Cells, 12(3), 400–409. https://doi.org/10.15283/IJSC18143
Sapudom, J., Wu, X., Chkolnikov, M., Ansorge, M., Anderegg, U., & Pompe, T. (2017). Fibroblast fate regulation by time dependent TGF-β1 and IL-10 stimulation in biomimetic 3D matrices. Biomaterials Science, 5(9), 1858–1867. https://doi.org/10.1039/c7bm00286f
Sargent, A., & Miller, R. H. (2016). MSC Therapeutics in Chronic Inflammation. Current Stem Cell Reports, 2(2), 168–173. https://doi.org/10.1007/s40778-016-0044-6
Seo, B. F., & Jung, S. N. (2016). The immunomodulatory effects of mesenchymal stem cells in prevention or treatment of excessive scars. Stem Cells International, 2016. https://doi.org/10.1155/2016/6937976
Singampalli, K. L., Balaji, S., Wang, X., Parikh, U. M., Kaul, A., Gilley, J., Birla, R. K., Bollyky, P. L., & Keswani, S. G. (2020). The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing. Frontiers in Cell and Developmental Biology, 8(July), 1–15. https://doi.org/10.3389/fcell.2020.00636
Singh, S., Young, A., & McNaught, C. E. (2017). The physiology of wound healing. Surgery (United Kingdom), 35(9), 473–477. https://doi.org/10.1016/j.mpsur.2017.06.004
Zhao, G., Liu, F., Liu, Z., Zuo, K., Wang, B., Zhang, Y., Han, X., Lian, A., Wang, Y., Liu, M., Zou, F., Li, P., Liu, X., Jin, M., & Liu, J. Y. (2020). MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing. Stem Cell Research and Therapy, 11(1), 1–18. https://doi.org/10.1186/s13287-020-01616-8
Consistently, A. V. (n.d.). Hypoxic Preconditioning of Mesenchymal Stromal Cells Induces Metabolic Changes , Enhances Survival , and Promotes Cell Retention In Vivo.
Gao, W., He, R., Ren, J., Zhang, W., Wang, K., Zhu, L., & Liang, T. (2021). Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway. FEBS Open Bio, 11(5), 1364–1373. https://doi.org/10.1002/2211-5463.13142
Han, C., Cheng, B., & Wu, P. (2020). Clinical guideline on topical growth factors for skin wounds. Burns & Trauma, 8. https://doi.org/10.1093/burnst/tkaa035
Ho, C. H., Lan, C. W., Liao, C. Y., Hung, S. C., Li, H. Y., & Sung, Y. J. (2018). Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model. Journal of the Chinese Medical Association, 81(3), 268–276. https://doi.org/10.1016/j.jcma.2017.03.013
Isakson, M., De Blacam, C., Whelan, D., McArdle, A., & Clover, A. J. P. (2015). Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential. Stem Cells International, 2015. https://doi.org/10.1155/2015/831095
King, A., Balaji, S., Le, L. D., & Crombleholme, T. M. (2014). Regenerative Wound Healing : The Role of Interleukin-10. 3(4), 315–323. https://doi.org/10.1089/wound.2013.0461
Li, Z., Wei, H., Deng, L., Cong, X., & Chen, X. (2010). Expression and secretion of interleukin-1β, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells. FEBS Journal, 277(18), 3688–3698. https://doi.org/10.1111/j.1742-4658.2010.07770.x
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25(4), 402–408. https://doi.org/10.1006/METH.2001.1262
Madrigal, M., Rao, K. S., & Riordan, N. H. (2014). A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. Journal of Translational Medicine, 12(1), 1–14. https://doi.org/10.1186/s12967-014-0260-8
Mazini, L., Rochette, L., Hamdan, Y., & Malka, G. (2021). Skin Immunomodulation during Regeneration: Emerging New Targets. Journal of Personalized Medicine 2021, Vol. 11, Page 85, 11(2), 85. https://doi.org/10.3390/JPM11020085
Motegi, S., & Ishikawa, O. (2016). Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. Journal of Dermatological Science. https://doi.org/10.1016/j.jdermsci.2016.11.005
Muhar, A. M., Putra, A., Warli, S. M., & Munir, D. (2019). Hypoxia-mesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Macedonian Journal of Medical Sciences. https://doi.org/10.3889/oamjms.2019.713
Nosenko, M. A., Ambaryan, S. G., & Drutskaya, M. S. (2019). Proinflammatory Cytokines and Skin Wound Healing in Mice. Molecular Biology, 53(5), 653–664. https://doi.org/10.1134/S0026893319050121
Numakura, S., Uozaki, H., Kikuchi, Y., Watabe, S., Togashi, A., & Watanabe, M. (2019). Mesenchymal stem cell marker expression in gastric cancer stroma. Anticancer Research, 39(1), 387–393. https://doi.org/10.21873/anticanres.13124
Oh, E. J., Lee, H. W., Kalimuthu, S., Kim, T. J., Kim, H. M., Baek, S. H., Zhu, L., Oh, J. M., Son, S. H., Chung, H. Y., & Ahn, B. C. (2018). In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model. Journal of Controlled Release, 279, 79–88. https://doi.org/10.1016/J.JCONREL.2018.04.020
Putra, A, Ridwan, F. B., Putridewi, A. I., Kustiyah, A. R., Wirastuti, K., Nac, S., & others. (2018). The role of tnf-α induced mscs on suppressive inflammation by increasing tgf-β and il-10. Open Access Maced J Med Sci, 610, 1779.
Putra, Agung. (2019). Hypoxia-preconditioned MSCs Have Superior Effect in Ameliorating Renal Function on Acute Renal Failure Animal Model. 1–6.
Sabry, D., Mohamed, A., Monir, M., & Ibrahim, H. A. (2019). The effect of mesenchymal stem cells derived microvesicles on the treatment of experimental CCL4 induced liver fibrosis in rats. International Journal of Stem Cells, 12(3), 400–409. https://doi.org/10.15283/IJSC18143
Sapudom, J., Wu, X., Chkolnikov, M., Ansorge, M., Anderegg, U., & Pompe, T. (2017). Fibroblast fate regulation by time dependent TGF-β1 and IL-10 stimulation in biomimetic 3D matrices. Biomaterials Science, 5(9), 1858–1867. https://doi.org/10.1039/c7bm00286f
Sargent, A., & Miller, R. H. (2016). MSC Therapeutics in Chronic Inflammation. Current Stem Cell Reports, 2(2), 168–173. https://doi.org/10.1007/s40778-016-0044-6
Seo, B. F., & Jung, S. N. (2016). The immunomodulatory effects of mesenchymal stem cells in prevention or treatment of excessive scars. Stem Cells International, 2016. https://doi.org/10.1155/2016/6937976
Singampalli, K. L., Balaji, S., Wang, X., Parikh, U. M., Kaul, A., Gilley, J., Birla, R. K., Bollyky, P. L., & Keswani, S. G. (2020). The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing. Frontiers in Cell and Developmental Biology, 8(July), 1–15. https://doi.org/10.3389/fcell.2020.00636
Singh, S., Young, A., & McNaught, C. E. (2017). The physiology of wound healing. Surgery (United Kingdom), 35(9), 473–477. https://doi.org/10.1016/j.mpsur.2017.06.004
Zhao, G., Liu, F., Liu, Z., Zuo, K., Wang, B., Zhang, Y., Han, X., Lian, A., Wang, Y., Liu, M., Zou, F., Li, P., Liu, X., Jin, M., & Liu, J. Y. (2020). MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing. Stem Cell Research and Therapy, 11(1), 1–18. https://doi.org/10.1186/s13287-020-01616-8
Authors
Ramadhanti, O. W. ., Putra, A., Sadyah, N. A. C., Prasetyowati, Hidayah, N., & Prasetyo, A. (2021). Perbandingan Pemberian Mesenchymal Stem Cell Hipoksia dan Normoksia Terhadap Ekspresi IL-10 pada Tikus Model Luka Eksisi. Journal of Midwifery and Health Science of Sultan Agung, 1(1), 20–27. https://doi.org/10.30659/jmhsa.v1i1.15
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