اثرات سلول‌های بنیادی مزانشیمی ژله وارتون به همراه صمغ درخت بنه در درمان آسیب‌های پوستی ناشی از سوختگی

محورهای موضوعی : مجله پلاسما و نشانگرهای زیستی

الهام حویزی ¹

1 - گروه زیست شناسی، دانشکده علوم، دانشگاه شهید چمران اهواز، اهواز، ایران

تاریخ دریافت : 1398/05/30 تاریخ پذیرش : 1399/02/20 تاریخ انتشار : 1399/04/01

کلید واژه: صمغ درخت بنه, مطالعات بافت‌شناسی, سلول‌های بنیادی ژله وارتون, سوختگی, سلول‌درمانی,

چکیده مقاله :

زمینه‌وهدف: سوختگی یکی از آسیب‌های رایج در جهان است که می توان از روش‌های نوین مانند سلول‌درمانی و طب سنتی برای درمان آن استفاده کرد. هدف از مطالعه‌ی حاضر بررسی اثرات ضمادی از صمغ بنه و روغن حیوانی به‌همراه سلول‌های بنیادی مزانشیمی ژله وارتون در درمان سوختگی درجه سه در رت‌های نژاد ویستار می‌باشد. روش‌کار: در این آزمایش تجربی، سلول‌های بنیادی از طریق جداسازی سلول‌های ژله وارتون از بندناف انسانی حاصل شد. برای انجام این مطالعه 28 رت بواسطه استامپ فلزی سوزانده و سپس به طور تصادفی در دو گروه کنترل(7 موش) و تیمار(21 موش) تقسیم شدند. گروه تیمار به سه دسته(هر گروه 7 موش) تیماربا ضماد، سلول‌درمانی و سلول‌درمانی بعلاوه ضماد تقسیم شدند. به هر رت تعداد 106 سلول در پاساژ سه و به‌صورت زیرجلدی تزریق شد. در روز 30 بعداز درمان آسان‌کشی با کلروفروم و تهیه‌ی مقاطع بافتی با رنگ‌آمیزی هماتوکسیلسن-ائوزین و تری‌کروم‌ماسون برای بررسی‌های میکروسکوپی صورت گرفت. یافته‌ها: مشاهدات میکروسکوپی نشان داد‌که در گروه‌های تیمار روند بهبودی با سرعت بالاتری نسبت گروه کنترل انجام گرفت. هم‌چنین بعد از گذشت 30 روز روش سلول‌درمانی+ ضماد به‌طور معنی‌داری موثرتر نسبت به ضماد و تزریق سلول به‌تنهایی بود. مطالعات بافت شناسی نشان دهنده‌ی ازدیاد معنی‌دار در آنژیوژنز، سنتز کلاژن، تعداد سلول‌ها، ضخامت لایه‌های پوست و در نهایت تسریع ترمیم زخم در نمونه‌های تیمار در مقایسه با نمونه‌های گروه کنترل بود. نتیجه‌گیری: براساس نتایج به‌دست آمده، روش‌های درمانی هم‌زمان استفاده شده در این مطالعه در تسریع ترمیم زخم‌های پوستی در مدل حیوانی به‌طور معنی‌داری تاثیر گذار بوده است.

چکیده انگلیسی:

Background: Burn is a common wound in the world and consider the novel methods such as cell therapy can be a helpful strategy in the treatment. The purpose of the present study is investigating the effects of using ointment of animal oil mixed with Gum of Pistacia atlantica associated wharton's jelly mesenchymal stem cells (WJMSCs) on rat third-degree burn models. Methods:In this experimental study, WJMSCs were extracted from human umbilical cord. For this study, 28 Wistar rats were burned by heating a metal rod of 1cm in diameter and then randomly divided into the control (7 rats) and treatment (21 rats) groups. The treatment group was divided into three groups (each group of 7 rats) of daily scrubbingof ointment, cell therapy, and cell therapy+ ointment. 106 cells (passage3) were injected into each rat subcutaneously. On day 30 after treatment, animals killed by chloroform and histological sections were prepared by staining Hematoxylsene-Eosin (H&E) and Trichromosone done for microscopic study. Results: Macroscopic and microscopic results indicated that in the experimental groups, the recovery was significantly more than the control. Also, the cell therapy+ ointment was significantly more effective than ointment and cell alone after 30 days. Histological analysis demonstrated a significant increase in angiogenesis, collagen synthesis, number of cells, thickness of skin layers, and totally acceleration wound healing in experimental groups compared to controls. Conclusion: Based on these data, it can be suggested that simultaneous cell-therapy and traditional medicine accelerate the repair of skin burns in the animal models more significantly.

منابع و مأخذ:

1.Akita, S., Hayashida, K., Yoshimoto, H., Fujioka, M., Senju, C., Morooka, S. (2017). Novel application of cultured epithelial autografts (CEA) with expanded mesh skin grafting over an artificial dermis or dermal wound bed preparation. International Journal of Molecular Sciences,19(1); 57.

2.Azizi, M., Ali Roozegar, Jalilian, F., Reza Havasian, M., Panahi, J., Pakzad, I. (2016). Antimicrobial effect of Pistacia atlantica leaf extract. Bioinformation,12(1); 19-21.

3.Aung, S.W., Abu Kasim, N.H., Ramasamy, T.S. (2019). Isolation, expansion, and characterization of wharton's jelly-derived mesenchymal stromal cell: method to identify functional passages for experiments. Methods Mol Biol, 2045; 323-335.

4.Bagheri, T., Fatemi, M.J., Hosseini, S.A., Mousavi, S.J., Araghi, S.h., Niazi, M. (2017). Investigating effect of ghee on treating second-degree burn wound in rats. Tehran University Medical Journal, 75(9); 645-652.

5.Benhassaini, H., El Zerey-Belaskri, A. (2016). Morphological leaf variability in natural populations of Pistacia atlantica Desf. subsp. atlantica along climatic gradient: new features to update Pistacia atlantica subsp. atlantica key. Int J Biometeorol, 60(4); 577-589.

6.Eyarefe, O., Amid, S. (2010). Small bowel wall response to enterotomy closure with polypropylene and polyglactin 910, using simple interrupted suture pattern in rats. International Journal of Animal and Veterinary Advances, 2(3); 72-75.

7.Hassan, W.U., Greiser, U., Wang, W. (2014). Role of adipose-derived stem cells in wound healing. Wound Repair And Regeneration, 22(3); 313-25.

8.Hu, J., Liu, N., Yang, X., Feng, Z., Qi, F. (2014) . Adiposed-derived stem cells seeded on PLCL/P123 eletrospun nanofibrous scaffold enhance wound healing. Biomedical Materials, 9(3); 70408-70420.

9.Hashemi, S.S., Mohammadi, A.A., Kabiri, H., Hashempoor, M.R., Mahmoodi, M., Amini, M. (2019). The healing effect of Wharton's jelly stem cells seeded on biological scaffold in chronic skin ulcers: A randomized clinical trial. J Cosmet Dermatol,18(6); 1961-1967.

10.Hoveizi, E., Tavakol, S. (2019). The rapeutic potential of human mesenchymal stem cells derived beta cell precursors on a nanofibrous scaffold: An approach to treat diabetes mellitus. J. Cell. Physiol., 234(7); 10196-10204.

11.Jaafari-Ashkvandi, Z., Shirazi, S. Y., Rezaeifard, S., Hamedi, A., Erfani, N. (2019). Cytotoxic effects of Pistacia atlantica (Baneh) fruit extract on human kb cancer cell line. Acta Medica (Hradec Kralove),62(1); 30-34.

12.Jing, B., Chen, W., Wang, M., Mao, X., Chen, J., Yu, X. (2019). Traditional tibetan ghee: physicochemical characteristics and fatty acid composition. J Oleo Sci., 4;68(9); 827-835

13.Julius, U. (2003). Influence of plasma free fatty acids on lipoprotein synthesis and diabetic dyslipidemia. [Review]. Exp Clin Endocrinol Diabetes, 111(5); 246-250.

14.Kamolz, L.P., Keck, M., Kasper C. (2014). Wharton's jelly mesenchymal stem cells promote wound healing and tissue regeneration. Stem. Cell. Res. Ther., 5(3); 62.

15.Kim, W.-S., Park, B.-S., Sung, J.-H., Yang, J.-M., Park, S.-B., Kwak, S.-J. (2007). Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. Journal of dermatological science, 48(1); 15-24.

16.Liu, P., Deng, Z., Han, S., Liu, T., Wen, N., Lu, W., Jin, Y. (2008). Tissue‐engineered skin containing mesenchymal stem cells improves burn wounds. Artificial organs, 32(12); 925-931.

17.Mahjoub, F., Akhavan Rezayat, K., Yousefi, M., Mohebbi, M., & Salari, R. (2018). Pistacia atlantica Desf. A review of its traditional uses, phytochemicals and pharmacology. [Review]. J Med Life, 11(3); 180-186.

18.Marchini, G., Pedrotti, E., Pedrotti, M., Barbaro, V., Di Iorio, E., Ferrari, S .(2012). Long‐term effectiveness of autologous cultured limbal stem cell grafts in patients with limbal stem cell deficiency due to chemical burns. Clinical & experimental ophthalmology, 40(3); 255-267.

19.Mathers, C. (2008). The global burden of disease: 2004 update. World Health Organization, 177(6); 919-929.

20.Nakagawa, H., Akita, S., Fukui, M., Fujii, T., & Akino, K. (2005). Human mesenchymal stem cells successfully improve skin‐substitute wound healing. British Journal of Dermatology, 153(1); 29-36.

21.Masmoei, B., Molazadeh, A., Kouhpayeh, S.A., Lohrasb, M.H., Najafipour, S., Alamdarloo, Y. (2014). The comparison of burn injury (second degree) recovery using silver sulphadiazine ointment 1% and the combination of mastic gum with ghee. Journal of Fasa University of Medical Sciences, 3 (4); 268-274.

22.Naudot, M., Barre, A., Caula, A., Sevestre H., Dakpe S., Mueller A.A. (2020). Co-transplantation of Wharton's jelly mesenchymal stem cell-derived osteoblasts with differentiated endothelial cells does not stimulate blood vessel and osteoid formation in nude mice models. J Tissue Eng Regen Med, 14(2); 257-271.

23.Nazempour, M., Mehrabani D., Mehdinavaz-Aghdam, R., Hashemi, S.S., Derakhshanfar, A., Zare, S. (2019). The effect of allogenic human Wharton's jelly stem cells seeded onto acellular dermal matrix in healing of rat burn wounds. J Cosmet Dermatol, doi: 10.1111/jocd.13109.

24.Obradovic, H., Krstic J., Trivanovic D., Mojsilovic S., Okic I., Kukolj T. (2019). Improving stemness and functional features of mesenchymal stem cells from Wharton's jelly of a human umbilical cord by mimicking the native, low oxygen stem cell niche. Placenta, 82; 25-34.

25.Peck, M. D. (2011). Epidemiology of burns throughout the world. Part I: Distribution and risk factors. Burns, 37(7); 1087-1100.

26.Pezeshki‐Modaress, M., Rajabi‐Zeleti, S., Zandi, M., Mirzadeh, H., Sodeifi, N., Nekookar, A. N. (2014). Cell‐loaded gelatin/chitosan scaffolds fabricated by salt‐leaching/lyophilization for skin tissue engineering: In vitro and in vivo study. Journal of Biomedical Materials Research Part A, 102(11); 3908-3917.

27.Varaa, N., Azandeh S., Khodabandeh Z., Gharravi, A.M. (2019). Wharton's Jelly Mesenchymal stem cell: various protocols for isolation and differentiation of hepatocyte-like cells; narrative review. Iran J Med Sci, 44(6):437-448.

28. Satheesan L., Soundian E., Kumanan V., Kathaperumal K. (2020). Potential of ovine Wharton jelly derived mesenchymal stem cells to transdifferentiate into neuronal phenotype for application in neuroregenerative therapy. Int J Neurosci, (2020);1-8.

29.Shokrgozar, M. A., Fattahi, M., Bonakdar, S., Ragerdi Kashani, I., Majidi, M., Haghighipour, N. (2012). Healing potential of mesenchymal stem cells cultured on a collagen-based scaffold for skin regeneration. Iran Biomed J, 16(2); 68-76.

30.Slavin, J. (1996). The role of cytokines in wound healing. The Journal of Pathology, 178(1); 5-10.

31.Tavakol, S., Azami, M., Khoshzaban, A., Ragerdi Kashani, I., Tavakol, B., Hoveizi, E., & Rezayat Sorkhabadi, S. M. (2013). Effect of laminated hydroxyapatite/gelatin nanocomposite scaffold structure on osteogenesis using unrestricted somatic stem cells in rat. [Research Support, Non-U.S. Gov't]. Cell Biol Int, 37(11), 1181-1189. doi: 10.1002/cbin.10143

32. Tettamanti, G., Grimaldi, A., Rinaldi, L., Arnaboldi, F., Congiu, T., Valvassori, R., & Eguileor, M. (2004). The multifunctional role of fibroblasts during wound healing in Hirudo medicinalis (Annelida, Hirudinea). Biology of the Cell, 96(6), 443-455.

33. Yuan, X.-q., Qiu, G., Liu, X.-j., Liu, S., Wu, Y., Wang, X., & Lu, T. (2012). Fluoxetine promotes remission in acute experimental autoimmune encephalomyelitis in rats. Neuroimmunomodulation, 19(4), 201-208.

34. Zeb, A., & Uddin, I. (2017). The Coadministration of Unoxidized and Oxidized Desi Ghee Ameliorates the Toxic Effects of Thermally Oxidized Ghee in Rabbits. J Nutr Metab, 2017, 4078360-407871.

35. Zohor, A.R., Shamsodini, S. (2004). Comparison of the regenerative effects of Ghee and silversolfodiazin in skin injury. Journal of Zanjan University, 39(10):21-24.

36. Zuliani, T., Saiagh, S., Knol, A.-C., Esbelin, J., & Dréno, B. (2013). Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. PLoS One, 24;8(7): e70408.