The effect of chitosan hydrogel containing the adipose derived mesenchymal stem cells on burn wound healing in rats

Document Type : Original Article

Authors

1 Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Hamedan Branch, Hamedan, Iran

2 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background and Objective: Cell therapy is one of the most challenging methods in the world in repairing burn wounds. The aim of this study was to determine the effect of chitosan hydrogel containing adipose-derived mesenchymal stem cells on burn wound healing in an animal model.
Materials and Methods: This study was performed experimentally using 24 Wistar rats. Burn wounds were created on the skin of rats and the animals were divided into two groups (control treated with normal saline) and the group treated with Chitosan hydrogel containing adipose tissue-derived mesenchymal stem cells. The healing process of burn wounds was evaluated quantitatively and qualitatively after treatment on days 7, 14 and 21 compared to the day 0. The data were analyzed using one-way analysis of variance.
Results: Concentration of 10% chitosan had no significant cytotoxic effect on mesenchymal stem cells and had proper consistency and clarity and SEM microscopy showed suitable porosity in chitosan. The expression of specific markers in mesenchymal stem cells and their potential for differentiation into adipocytes and bone cells confirmed the mesenchymal nature of the cells. Wound area on days 7, 14 and 21 in the chitosan-treated group containing mesenchymal cells was significantly smaller than the control group.
Conclusion: Mesenchymal stem cells transferred by chitosan to the wound site cause accelerated healing of burn wound and therefore, it is important to evaluate the use of this dressing in the healing of burn wounds in patients.

Keywords


  1. Lateef H, Abatan OI, Aslam MN, Stevens MJ, Varani J. Topical pretreatment of diabetic rats with all-trans retinoic acid improves healing of subsequently induced abrasion wounds. American Diabetes Association 2005;54(3):855-61.‏
  2. Moura LI, Dias AM, Carvalho E, de Sousa HC. Recent advances on the development of wound dressings for diabetic foot ulcer treatment—a review. Acta Biomaterialia 2013;9(7):7093-114.
  3. Lv FJ, Tuan RS, Cheung KM, Leung VY. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem cells Research 2014;32(6):1408-19.
  4. Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O. Role of pericytes in skeletal muscle regeneration and fat accumulation. Stem Cells and Development 2013;22(16):2298-314.
  5. Lim KH, Itinteang T, Davis PF, Tan ST. Stem Cells in Keloid Lesions: A Review. Plastic and Reconstructive Surgery Global Open 2019;7(5):e2228.
  6. Falanga V, Iwamoto S, Chartier M, Yufit T, Butmarc J, Kouttab N, et al. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Engineering 2007;13(6):1299–312.
  7. Mansilla E, Marin GH, Sturla F, et al. Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplantation Proceeding 2005;37(1):292‐294.
  8. Maharlooei MK, Bagheri M, Solhjou Z, Jahromi BM, Akrami M, Rohani L, et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice 2011;93(2):228-234.
  9. Kim WS, Park BS, Sung JH. The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin on Biological Therapy 2009;9(7):879–887.
  10. Thakur S, Govender PP, Mamo MA, Tamulevicius S, Thakur VK. Recent progress in gelatin hydrogel nanocomposites for water purification and beyond. Vacuum 2017;146:396-408.
  11. Ishida K, Kuroda R, Miwa M, Tabata Y, Hokugo A, Kawamoto T, Sasaki K, Doita M, Kurosaka M. The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Engineering. 2007;13(5):1103-1112.
  12. Hokugo A, Ozeki M, Kawakami O, Sugimoto K, Mushimoto K, Morita S, Tabata Y. Augmented bone regeneration activity of platelet-rich plasma by biodegradable gelatin hydrogel. Tissue Engineering 2005;11(7-8):1224-1233.
  13. Yang G, Xiao Z, Long H, Ma K, Zhang J, Ren X, Zhang J. Assessment of the characteristics and biocompatibility of gelatin sponge scaffolds prepared by various crosslinking methods. Scientific Reports 2018 25;8(1):1-3.
  14. Sisakht MM, Nilforoushzadeh MA, Verdi J, Banafshe HR, Naraghi ZS, Mortazavi-Tabatabaei SA. Fibrin-collagen hydrogel as a scaffold for dermoepidermal skin substitute, preparation and characterization. Journal of Contemporary Journal of Contemporary Medical Sciences 2019;5(1).
  15. Nie C, Yang D, Xu J, Si Z, Jin X, Zhang J. Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplantation 2011;20(2):205-16.
  16. Wu M, Zhang R, Zou Q, Chen Y, Zhou M, Li X, Ran R, Chen Q. Comparison of the biological characteristics of mesenchymal stem cells derived from the human placenta and umbilical cord. Scientific Reports 2018 22;8(1):1-9.
  17. Yang G, Xiao Z, Long H, Ma K, Zhang J, Ren X, Zhang J. Assessment of the characteristics and biocompatibility of gelatin sponge scaffolds prepared by various crosslinking methods. Scientific Reports 2018 25;8(1):1-3.
  18. Yang G, Xiao Z, Long H, Ma K, Zhang J, Ren X, Zhang J. Assessment of the characteristics and biocompatibility of gelatin sponge scaffolds prepared by various crosslinking methods. Scientific Reports 2018 25;8(1):1-3.
  19. Kouhbananinejad SM, Derakhshani A, Vahidi R, Dabiri S, Fatemi A, Armin F, Farsinejad A. A fibrinous and allogeneic fibroblast-enriched membrane as a biocompatible material can improve diabetic wound healing. Biomaterials Science 2019;7(5):1949-61.
  20. Kouhbananinejad SM, Derakhshani A, Vahidi R, Dabiri S, Fatemi A, Armin F, Farsinejad A. A fibrinous and allogeneic fibroblast-enriched membrane as a biocompatible material can improve diabetic wound healing. Biomaterials Science 2019;7(5):1949-61.
  21. Amiel SA, Aschner P, Childs B, Cryer PE, de Galan BE, Frier BM, Gonder-Frederick L, Heller SR, Jones T, Khunti K, Leiter LA. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. The Lancet Diabetes & Endocrinology 2019;7(5):385-96.
  22. Esteghamati A, Larijani B, Aghajani MH, Ghaemi F, Kermanchi J, Shahrami A, Saadat M, Esfahani EN, Ganji M, Noshad S, Khajeh E. Diabetes in Iran: prospective analysis from first nationwide diabetes report of National Program for Prevention and Control of Diabetes (NPPCD-2016). Scientific Reports 2017;7(1):1-0.
  23. Cao Y, Gang X, Sun C, Wang G. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer. Journal of Diabetes Research 2017;2017:9328347.
  24. Roşca AM, Ţuţuianu R, Titorencu ID. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Romanian Journal of morphology and Embryology 2018;59(3):655-662.
  25. Guo J, Hu H, Gorecka J, et al. Adipose-derived mesenchymal stem cells accelerate diabetic wound healing in a similar fashion as bone marrow-derived cells. American Journal of Physiology. Cell Physiology 2018;315(6):C885-C896.
  26. Maharlooei MK, Bagheri M, Solhjou Z, Moein Jahromi B, Akrami M, Rohani L, et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice 2011;93(2):228‐234.
  27. Liu R, Chang W, Li J, et al. Mesenchymal stem cells in psoriatic lesions affect the skin microenvironment through circular RNA. Experimental Dermatology 2019;28(3):292‐299.
  28. Kosaric N, Kiwanuka H, Gurtner GC. Stem cell therapies for wound healing. Expert Opinion on Biological Therapy 2019;19(6):575-585.
  29. Badillo Andrea T, Redden Robert A , Zhang Liping , Doolin Edward J, Liechty Kenneth W. Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure. Cell and Tissue Research 2007; 329: 301-311.
  30. Saheli M, Hosseini A, Piryaei A, Fadaei Fathabadi F, Bandehpour M, Salehi M, Norouzian M. Evaluation of the differentiation process of human bone marrow mesenchymal stem cells to cardiomyocyte-like cells: An in vitro study. Journal of Iranian Anatomical Sciences 2011; 9: 179-90.
  31. Wu Y, Chen L, Scott PG, Tredget EE. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 2007;25(10):2648-59.
  32. Gomez – Guillen M.C, Girmenez B, Lopez – Caballero M.E, Montero M.P. Functional and bioactive properties of Collagen and gelatin from alternative sources: A review. Food Hydrocolloids 2011;25(8):1813-27.