The effect of spraying the suspension containing adipose derived mesenchymal stem cells on diabetic wound healing and collagen synthesis in skin tissue in an animal model

Document Type : Original Article

Authors

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

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

3 Department of Medical Immunology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background and Objective: Although many studies have been performed concerning the effects of adipose-derived mesenchymal stem cells on wound healing, the repairing effects of these cells are still controversial. In this context, the present study investigated the effect of spraying the adipose-derived mesenchymal stem cells suspension on diabetic wound healing and skin tissue collagen synthesis in an animal model.
Materials and Methods: In this experimental study, abdominal adipose tissue was obtained from patients referred for abdominoplasty. Mesenchymal cells were isolated from adipose tissue and identified by micoscoic examination and flow cytometry. Streptozotocin was used to induce diabetes in 10 male Wistar rats. Wounds with a diameter of 0.8 cm were created by a biopsy punch in the back of diabetic rats. Animals were divided into two groups: control (untreated) and treated with mesenchymal cell. After treatment, wound healing was assessed by photographic methods on days 7, 14 and 21 and the collagen synthesis was evaluated using Mason’s trichrome method.
Results: Observational data showed that the wound healing rate was higher in the treatment group than control group. 21 days after treatment, the density of collagen fibers, the formation of tissue vessels and the collagen fibers arrangement had higher quality in the treatment group than the control group.
Conclusion: Spraying the adipose-derived mesenchymal stem cells in diabetic wound area can increase the collagen synthesis in the wound area and accelerate the healing of the diabetic wound. According to which, the use of these cells can be considered in cell therapy of wounds.

Keywords


  1. Sharma R, Sharma SK, Mudgal SK, Jelly P, Thakur K. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Scientific Reports  2021;11(1):1-2. doi:10.1038/s41598-021-81886-1.
  2. Khalilifar MA, Eslaminejad MB, Ghasemzadeh M, Hosseini S, Baharvand H. In vitro and in vivo comparison of different types of rabbit mesenchymal stem cells for cartilage repair. Cell Journal 2019;21(2):150. doi: 10.22074/cellj.2019.6149.
  3. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Annals of Medicine 2017;49(2):106-16. doi: 10.1080/07853890.2016.1231932.
  4. Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the management of diabetic foot ulcer. World Journal of Diabetes 2015;6(1):37. doi: 10.4239/wjd.v6.i1.37.
  5. Kucharzewski M, Rojczyk E, Wilemska-Kucharzewska K, Wilk R, Hudecki J, Los MJ. Novel trends in application of stem cells in skin wound healing. European Journal of Pharmacology 2019;843:307-15. doi: 10.1016/j.ejphar.2018.12.012.
  6. Chen CY, Wu RW, Hsu MC, Hsieh CJ, Chou MC. Adjunctive hyperbaric oxygen therapy for healing of chronic diabetic foot ulcers. Journal of Wound, Ostomy and Continence Nursing 2017;44(6):536-45. doi: 10.1097/WON.0000000000000374.
  7. Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, et al. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 2012;33(29):7008-18. doi:10.1016/j.biomaterials.2012.06.058.
  8. Lin W, Li HY, Yang Q, Chen G, Lin S, Liao C, Zhou T. Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis. Stem Cell Research & Therapy 2021;12(1):1-21. doi:/10.1186/s13287-020-02108-5.
  9. Torre PD, Flores AI. Current status and future prospects of perinatal stem cells. Genes 2021;12(1):6. doi: 10.3390/genes12010006.
  10. 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. doi:10.1634/stemcells.2007-0226.
  11. Kosaric N, Kiwanuka H, Gurtner GC. Stem cell therapies for wound healing. Expert Opinion on Biological Therapy 2019;19(6):575-85. doi:10.1080/14712598.2019.1596257.
  12. Álvaro-Afonso FJ, Sanz-Corbalán I, Lázaro-Martínez JL, Kakagia D, Papanas N. Adipose-derived mesenchymal stem cells in the treatment of diabetic foot ulcers: a review of preclinical and clinical studies. Angiology 2020;71(9):853-63. doi./10.1177/0003319720939467.
  13. Souza CM, Mesquita LA, Souza D, Irioda AC, Francisco JC, Souza CF, et al. Regeneration of skin tissue promoted by mesenchymal stem cells seeded in nanostructured membrane. In Transplantation Proceedings 2014; 46( 6): 1882-1886). Elsevier. doi.org/10.1016/j.transproceed.2014.05.066.
  14. Juncosa-Melvin N, Matlin KS, Holdcraft RW, Nirmalanandhan VS, Butler DL. Mechanical stimulation increases collagen type I and collagen type III gene expression of stem cell–collagen sponge constructs for patellar tendon repair. Tissue Engineering 2007;13(6):1219-26. doi:10.1089/ten.2006.0339.
  15. Meruane MA, Rojas M, Marcelain K. The use of adipose tissue–derived stem cells within a dermal substitute improves skin regeneration by increasing neoangiogenesis and collagen synthesis. Plast. Journal of Surgical Reconstruction 2012;130(1):53-63. doi: 10.1097/PRS.0b013e3182547e04.
  16. Ghaneialvar H, Arjmand S, Sahebghadam Lotfi A, Soleimani M, Mashhadi Abbas F. Influence of adipose derived mesenchymal stem cells on the effective inflammatory factors of diabetic wound healing in animal models. Journal of Mazandaran University of Medical Sciences 2017;27(148):12-21.
  17. Mehrbani Azar Y, Green R, Niesler CU, van de Vyver M. Antioxidant preconditioning improves the paracrine responsiveness of mouse bone marrow mesenchymal stem cells to diabetic wound fluid. Stem Cells and Development 2018;27(23):1646-57.
  18. Mizuno H, Tobita M, Orbay H, Uysal AC, Lu F. Adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells and Cancer Stem Cells 2014: 12:165-74. doi: 10.1007/978-94-017-8032-2_15.
  19. Yang HY, Fierro F, So M, Yoon DJ, Nguyen AV, Gallegos A, et al. Combination product of dermal matrix, human mesenchymal stem cells, and timolol promotes diabetic wound healing in mice. Stem Cells Translational Medicine 2020;9(11):1353-64. doi: 10.1002/sctm.19-0380.
  20. Wan J, Xia L, Liang W, Liu Y, Cai Q. Transplantation of bone marrow-derived mesenchymal stem cells promotes delayed wound healing in diabetic rats. Journal of Diabetes Research 2013;2013. doi: 10.1155/2013/647107.
  21. Shevchenko RV, James SL, James SE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. Journal of the Royal Society Interface 2010;7(43):229-58. doi:10.1098/rsif.2009.0403.
  22. Ong HT, Dilley RJ. Novel non-angiogenic role for mesenchymal stem cell-derived vascular endothelial growth factor on keratinocytes during wound healing. Cytokine & Growth Factor Reviews 2018; 44:69-79. doi: 10.1016/j.cytogfr.2018.11.002.
  23. Xie Z, Hao H, Tong C, Cheng Y, Liu J, Pang Y, et al. Human umbilical cord‐derived mesenchymal stem cells elicit macrophages into an anti‐inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats. Stem Cells 2016;34(3):627-39. doi: 10.1002/stem.2238.
  24. Chen Z, Wang Y, Shi C. Therapeutic implications of newly identified stem cell populations from the skin dermis. Cell Transplantation 2015;24(8):1405-22. doi: 10.3727/096368914X682431.
  25. Kosaric N, Kiwanuka H, Gurtner GC. Stem cell therapies for wound healing. Expert Opinion on Biological Therapy 2019 ;19(6):575-85. doi: 10.1080/14712598.2019.1596257.
  26. Brindo da Cruz IC, Velosa AP, Carrasco S, dos Santos Filho A, Tomaz de Miranda J, Pompeu E, et al. Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage. Front. Frontiers in Cell and Developmental Biology 2021; 9:539. doi: 10.3389/fcell.2021.606890.
  27. Shokrgozar MA, Fattahi M, Bonakdar S, Kashani IR, Majidi M, Haghighipour N, et al. Healing potential of mesenchymal stem cells cultured on a collagen-based scaffold for skin regeneration. Iran. Biomedical Journal 2012;16(2):68. doi: 10.6091/ibj.1053.2012.
  28. Gadelkarim M, Abushouk AI, Ghanem E, Hamaad AM, Saad AM, Abdel-Daim MM. Adipose-derived stem cells: effectiveness and advances in delivery in diabetic wound healing. Biomed. Pharmacother 2018;107:625-33. doi: 10.1016/j.biopha.2018.08.013.
  29. Yu S, Cheng Y, Zhang L, Yin Y, Xue J, Li B, et al. Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats. Stem Cell Research & Therapy 2019; 10(1):1-8. doi: 10.1186/s13287-019-1474-8.