Clinical and Histopathological Study of the Effect of Adipose-Derived Mesenchymal Stem Cells on Corneal Neovascularization following Alkali Burn in a Rabbit Model

Document Type : Original Articles


College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq


The cornea, the transparent part of the eye, performs a significant function in eyesight by refracting the light to focus a visual image. Since the cornea is indispensable for vision, corneal inflammation may induce visual disturbance and blindness. Several investigations have reported that various corneal inflammatory diseases cause visual impairment and chronic inflammation of the cornea, which can lead to blindness. The present study aimed to assess the effect of adipose-derived mesenchymal stem cells (ADMSCs) on corneal healing after alkali injuries. Corneal alkali injuries were induced in the eyes of 20 rabbits. The MSC group (n=10) was treated with subconjunctival injections, while the control group (n=10) was left without any treatment. Rabbits underwent slit-lamp examination and photography and were evaluated for corneal neovascularization. Based on the histological evaluation, the eyes treated with MSCs showed better recovery. Furthermore, the MSC and control groups were significantly different in the degree of corneal neovascularization and re-epithelialization, as well as the elevation of the neovascular tissue at two and four weeks post-surgery.


Main Subjects

  1. Wang H, Zhang Y, Li Z, Wang T, Liu P. Prevalence and causes of corneal blindness. Clin Experiment Ophthalmol. 2014;42(3):249-53.
  2. Perez V, Saeed A, Tan Y, Urbieta M, Cruz-Guilloty F. The eye: a window to the soul of the immune system. J Autoimmun. 2013;45:7-14.
  3. Ellenberg D, Azar DT, Hallak JA, Tobaigy F, Han KY, Jain S, et al. Novel aspects of corneal angiogenic and lymphangiogenic privilege. Prog Retin Eye Res. 2010;29(3):208-48.
  4. Kao W-Y, Zhu G, Benza R, Kao C-C, Ishizaki M, Wander A. Appearance of immune cells and expression of MHC II DQ molecule by fibroblasts in alkali-burned corneas. Ophthalmic Lit. 1997;1(50):7.
  5. Brodovsky SC, McCarty CA, Snibson G, Loughnan M, Sullivan L, Daniell M, et al. Management of alkali burns: an 11-year retrospective review. Ophthalmology. 2000;107(10):1829-35.
  6. Ye J, Yao K, Kim J. Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye. 2006;20(4):482-90.
  7. DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37(3):588-98.
  8. Wagoner MD. Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol. 1997;41(4):275-313.
  9. Liu G, Wu H, Lu P, Zhang X. Interleukin (IL)-17A promotes angiogenesis in an experimental corneal neovascularization model. Curr Eye Res. 2017;42(3):368-79.
  10. Tzeng H-E, Tsai C-H, Chang Z-L, Su C-M, Wang S-W, Hwang W-L, et al. Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. Biochem Pharmacol. 2013;85(4):531-40.
  11. Zannettino A, Paton S, Arthur A, Khor F, Itescu S, Gimble J, et al. Multipotential human adipose‐derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol. 2008;214(2):413-21.
  12. Hoogduijn M, Crop M, Peeters A, Van Osch G, Balk A, Ijzermans J, et al. Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev. 2007;16(4):597-604.
  13. Oh W, Kim D-S, Yang YS, Lee JK. Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol. 2008;251(2):116-23.
  14. Su WR, Zhang QZ, Shi SH, Nguyen AL, Le AD. Human gingiva‐derived mesenchymal stromal cells attenuate contact hypersensitivity via prostaglandin E2‐dependent mechanisms. Stem Cells. 2011;29(11):1849-60.
  15. Oh JY, Kim MK, Shin MS, Lee HJ, Ko JH, Wee WR, et al. The anti‐inflammatory and anti‐angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells. 2008;26(4):1047-55.
  16. Karathanasis V, Petrakis S, Topouridou K, Koliakou E, Koliakos G, Demiri E. Intradermal injection of GFP-producing adipose stromal cells promotes survival of random-pattern skin flaps in rats. Eur J Plast Surg. 2013;36(5):281-8.
  17. Eesa M, Omar R, Nazht H, Al-Badrawi T. Evaluation of general anaesthesia by using Propionylpromazine, Xylazine and Ketamine in rabbits. Iraq J Vet Med. 2010;34(1):208-17.
  18. Frieedenstein A, Petrakova K, Kurolesova A, Frolova G. Hetrotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoetic tissue. Transplantacion. 1968;6(2):230.
  19. He Q, Wan C, Li G. Concise review: multipotent mesenchymal stromal cells in blood. Stem cells. 2007;25(1):69-77.
  20. Polisetty N, Fatima A, Madhira SL, Sangwan VS, Vemuganti GK. Mesenchymal cells from limbal stroma of human eye. Mol Vis. 2008;14:431.
  21. Yao L, Bai H. Mesenchymal stem cells and corneal reconstruction. Mol Vis. 2013;19:2237.
  22. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276(5309):71-4.
  23. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic propertiesof differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890-6.
  24. Pirounides D, Komnenou A, Papaioannou N, Gounari E, Stylianaki I, Alexandridis A, et al. The antiangiogenic properties of adipose-derived mesenchymal stem/stromal cells in corneal neovascularization in a rabbit model. Med. Hypothesis Discov Innov Ophthalmol. 2020;9(2):74.
  25. Liu H, Zhang J, Liu C-Y, Wang I-J, Sieber M, Chang J, et al. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice. PloS one. 2010;5(5):e10707.
  26. Yao L, Li Z-r, Su W-r, Li Y-p, Lin M-l, Zhang W-x, et al. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn. PLoS one. 2012;7(2):30842.
  27. Zajicova A, Pokorna K, Lencova A, Krulova M, Svobodova E, Kubinova S, et al. Treatment of ocular surface injuries by limbal and mesenchymal stem cells growing on nanofiber scaffolds. Cell Transplant. 2010;19(10):1281-90.
  28. Ghazaryan E, Zhang Y, He Y, Liu X, Li Y, Xie J, et al. Mesenchymal stem cells in corneal neovascularization: Comparison of different application routes. Mol Med Rep. 2016;14(4):3104-12.
  29. Oh JY, Roddy GW, Choi H, Lee RH, Ylöstalo JH, Rosa RH, et al. Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury. Proc Natl Acad Sci. 2010;107(39):16875-80.
  30. Bronckaers A, Hilkens P, Martens W, Gervois P, Ratajczak J, Struys T, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther. 2014;143(2):181-96.