Evaluation of therapeutic potential of bone marrow hematopoietic stem cells in diabetic wound healing

Authors

Abstract

Background and Objective: Cell therapy is one of the attractive and novel approaches in the treatment of chronic wounds. The aim of this study was to evaluate the function of bone marrow derived hematopoietic stem cells (CD93) in the treatment of diabetic ulcers.
 
Materials and Methods: In this study, 15 BALB/c strain mice, weighing 25-30 g were used, of which 10 were made diabetic by streptozotocin (STZ). Circular skin lesions 6 mm in diameter and 2 mm depth were created in the skin of mice. Studied mice were divided into 3 groups including normal mice without diabetes (sham), diabetic mice without transplanted CD93 cells (Control) and diabetic mice that underwent CD93 cell transplantation twice (density of cells: 1 × 107). The parameters of wound area, wound healing, differentiation and survival of CD93 cells were calculated on days 7, 14 and 28 after cell transplantation using the fluorescent microscope and DiL labeling antibody with Image J and SPSS softwares.
 
Results: The most difference in the level and rate of healing was related to cell group and the control group, respectively (p <0.05 and p <0.01). Immunohistochemical study of CD93 marker showed viability and activity of stem cells at the wound site until 28 days after transplantation.
 
Conclusion: CD93 stem cell transplantation significantly accelerated diabetic wound healing process and these cells are introduced as an appropriate option for diabetic wounds cell therapy.

Keywords


1. Wild S, Roglic G, Green A, Sicree R, King H. RoglicGlobal prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5): 1047-1053. 2. Fazeli FS, van der Aa MP, van der Vorst MM, Knibbe CA, de Boer A. Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: A systematic review and evaluation of methodological approaches. Diabetologia 2013; 56(7):1471–1488. 3. Holstein P, Ellitsgaard N, Olsen BB, Ellitsgaard V. Decreasing incidence of major amputations in people with diabetes. Diabetologia 2000; 43(7):844–847. 4. Jeffcoate WJ, Price PE, Phillips CJ, Game FL, Mudge E, Davies S, et al. Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes. Health Technology Assessment 2009; 13(54):1-110. 5. Jude EB, Apelqvist, Spraul M, Martini J. Prospective randomized controlled study of Hydrofiber dressing containing ionic silver or calcium alginate dressings in non-ischaemic diabetic foot ulcers. Diabetic Medicine 2007; 24(3): 280-8. 6. Greaves NS, Iqbal SA, Baguneid M, Bayat A. The role of skin substitutes in the management of chronic cutaneous wounds. Wound Repair Regen 2013; 21(2): 194–210. 7. 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 Biomater 2013; 9(7): 7093–7114. 8. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 2005; 366(9498): 1736–1743. 9. Brem H, Sheehan P, Rosenberg HJ, Schneider JS, Boulton AJ. Evidence-based protocol for diabetic foot ulcers. Plastic and Reconstructive Surgery 2006; 117(7): 193-209. 10. Nwomeh, B. C.; Yager, D. R.; Cohen, I. K. Physiology of the chronic wound. Clinics in Plastic Surgery 1998; 25(3): 341–356. 11. Yang, M.; Sheng, L.; Zhang, T. R.; Li, Q. Stem cell therapy for lower extremity diabetic ulcers: Where do we stand?. BioMed Research International 2013; 2013: 1-8. 12. Dimarino, A. M.; Caplan, A. I.; Bonfield, T. L. Mesenchymal stem cells in tissue repair. Front. Immunol 2013; 4: 1-9. 13. Weissman I L, Stem cells: units of development, units of regeneration, and units in evolution. Cell 2000; 100(1): 157-168. 14. Borue X1, Lee S, Grove J, Herzog EL, Harris R, Diflo T. Bone marrow-derived cells contribute to epithelial engraftment during wound healing. The American Journal of Pathology 2004; 165(5): 1767-1772. 15. Cha J, Falanga V. Stem cells in cutaneous wound healing. Clinics in Dermatology 2007; 25(1): 73-78 16. Nakagawa H1, Akita S, Fukui M, Fujii T, Akino K. Human mesenchymal stem cells successfully improve skin substitute wound healing. The British Journal of Dermatology 2005; 153(1): 29-36. 17. Ichioka S1, Kouraba S, Sekiya N, Ohura N, Nakatsuka T. Bone marrow-impregnated collagen matrix for wound healing: experimental evaluation in a microcirculatory model of angiogenesis, and clinical experience. British Journal of Plastic Surgery 2005; 58(8): 1124-1130. 18. Wettstein R, Savic M, Pierer G, ScheufleR O, Haug M, HalteR J. Progenitor cell therapy for sacral pressure sore: a pilot study with a novel human chronic wound model. Stem Cell Research & Therapy 2014; 5(1): 5-18. 19. Maharlooei M, Bagheri M, Solhjou Z, Jahromi B, Akrami M, et al. Adipose tissue derived mesenchymal stem cell promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice 2011; 93: 228-234. 20. Cavanagh P R, Lipsky BA, Bradbury AW, Botek G. Treatment for diabetic foot ulcers. Lancet 2005; 366(9498): 1725–1735. 21. Kim, J. Y. and W. Suh. Stem cell therapy for dermal wound healing. Journal of Stem Cells 2010; 3(1): 29. 22. Barcelos LS1, Duplaa C, Kränkel N, Graiani G, Invernici G, Katare R, et al. Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling. Circulation Research 2009; 104(9): 1095-1102. 23. Cha J, Falanga V. Stem cells in cutaneous wound healing. Clinics in Dermatology 2007; 25(1): 73-78. 24. Shumakov VI1, Onishchenko NA, Rasulov MF, Krasheninnikov ME, Zaidenov VA. Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts. Bulletin of Experimental Biology and Medicine 2003; 136(2): 192-195. 25. Chen L, Tredget EE, Wu PY, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PloS One 2008; 3(4): e1886. 26. Borue X1, Lee S, Grove J, Herzog EL, Harris R, Diflo T. Bone marrow-derived cells contribute to epithelial engraftment during wound healing. American Journal of Pathology 2004; 165(5): 1767-1772.