Document Type : Original paper
1 Department of Obstetrics and Gynecology, Faculty of Health Sciences, Medical University of Lublin, Poland
2 Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
3 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
Background and aim: Although many studies suggest that conditioned medium derived from stem cells can be effective in wound healing, the results are still challenging. Accelerating the wound healing in diabetic patients is one the most important topics currently being discussed. The aim of the research is to investigate the effects of conditioned medium derived from neonatal fibroblast cells on diabetic wound healing in male rats. Materials and methods: Neonatal fibroblast cells were isolated from foreskin and cultured in DMEM culture medium. Conditioned medium was harvested. Male rats were divide into control (without treatment) and experiment (treatment with conditioned medium) groups (n=5 in each group). Diabetes was induced in animals by intraperitoneal injection of streptozotocin (150 mg/kg), and a full-thickness skin defect model was generated. Wound healing was evaluated 7, 14 and 21 days after treatment using Image J software. Results: Significant decrease in wound area was observed only at 21 days after treatment in control group; However, wound area was significantly decreased 14 and 21 days after treatment compared to the day 0. Conclusion: Our findings show that the conditioned medium derived from neonatal fibroblast cells isolated for foreskin has accelerating effects on diabetic wound healing in animal model.
. Glovaci D, Fan W, Wong ND. Epidemiology of diabetes mellitus and cardiovascular disease. Current cardiology reports. 2019;21(4):1-8.
. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JC, Mbanya JC, Pavkov ME. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes research and clinical practice. 2022;183:109119.
. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014;37(Supplement_1):S81-90.
. Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62(1):3-16.
. Zhang S, Chen L, Zhang G, Zhang B. Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages.Stem cell research & therapy. 2020;11(1):1-5.
. Saedi E, Gheini MR, Faiz F, Arami MA. Diabetes mellitus and cognitive impairments. World journal of diabetes. 2016;7(17):412.
. McGrath JA. Wound healing. In: Breathnach SM. Textbook of dermatology. 7th ed. New York: Blackwell; 2004;1-11,250.
. Nern K. Dermatologic conditions associated with diabetes. Current diabetes reports. 2002;2(1):53-9.
. Singh J, Kakkar P. Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. Journal of ethnopharmacology. 2009;123(1):22-6.
. Álvaro-Afonso FJ, García-Álvarez Y, Lázaro-Martínez JL, Kakagia D, Papanas N. Advances in dermoepidermal skin substitutes for diabetic foot ulcers. Current vascular pharmacology. 2020;18(2):182-92.
. Boulton AJ. The diabetic foot. Medicine. 2019;47(2):100-5.
. Shams K. The Effects of Fibroblast-Conditioned Medium Isolated from Human Neonatal Foreskin on Diabetic Ulcers in Rats. 2021.
. Xin Y, Xu P, Wang X, Chen Y, Zhang Z, Zhang Y. Human foreskin-derived dermal stem/progenitor cell-conditioned medium combined with hyaluronic acid promotes extracellular matrix regeneration in diabetic wounds. Stem Cell Research & Therapy. 2021;12(1):1-8.
. Toma JG, Akhavan M, Fernandes KJ, Barnabé-Heider F, Sadikot A, Kaplan DR, Miller FD. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature cell biology. 2001;3(9):778-84.
. Sun J, Zhang Y, Song X, Zhu J, Zhu Q. The healing effects of conditioned medium derived from mesenchymal stem cells on radiation-induced skin wounds in rats. Cell transplantation. 2019;28(1):105-15.
. Shrestha C, Zhao L, Chen K, He H, Mo Z. Enhanced healing of diabetic wounds by subcutaneous administration of human umbilical cord-derived stem cells and their conditioned media. International journal of endocrinology. 2013;2013.
. Li Y, Xia WD, Van der Merwe L, Dai WT, Lin C. Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies. Stem cell research & therapy. 2020;11(1):1-2.
. Maksimova N, Krasheninnikov M, Zhang Y, Ponomarev E, Pomytkin I, Melnichenko G,
Lyundup A. Early passage autologous mesenchymal stromal cells accelerate diabetic wound reepithelialization: a clinical case study. Cytotherapy. 2017;19(12):1548-50.
. Ahangar P, Mills SJ, Smith LE, Strudwick XL, Ting AE, Vaes B, Cowin AJ. Human multipotent adult progenitor cell-conditioned medium improves wound healing through modulating inflammation and angiogenesis in mice. Stem cell research & therapy. 2020;11(1):1-6.
. Montero-Vilchez T, Sierra-Sánchez Á, Sanchez-Diaz M, Quiñones-Vico MI, Sanabria-dela-Torre R, Martinez-Lopez A, Arias-Santiago S. Mesenchymal stromal cell-conditioned medium for skin diseases: A systematic review. Frontiers in cell and developmental biology. 2021;9.
. Lamme EN, van Leeuwen RT, Jonker A, van Marle J, Middelkoop E. Living skin substitutes: survival and function of fibroblasts seeded in a dermal substitute in experimental wounds. Journal of investigative dermatology. 1998;111(6):989-95.
. Deng Q, Huang S, Wen J, Jiao Y, Su X, Shi G, Huang J. PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice. Stem cell research & therapy. 2020;11(1):1-5.
. Saheli M, Bayat M, Ganji R, Hendudari F, Kheirjou R, Pakzad M, Najar B, Piryaei A. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Archives of dermatological research. 2020;312(5):325-36.
. Dong L, Hao H, Liu J, Ti D, Tong C, Hou Q, Li M, Zheng J, Liu G, Fu X, Han W. A conditioned medium of umbilical cord mesenchymal stem cells overexpressing Wnt7a promotes wound repair and regeneration of hair follicles in mice. Stem cells international. 2017;2017.
. Houreld NN, Ayuk SM, Abrahamse H. Cell adhesion molecules are mediated by photobiomodulation at 660 nm in diabetic wounded fibroblast cells. Cells. 2018;7(4):30.
. Montesano R, Orci L. Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proceedings of the National Academy of Sciences. 1988;85(13):4894-7