Ünal BIÇAKCI, Berat Dilek DEMİREL, Oğuz AYDIN, Rıza RIZALAR, Ferda ALPASLAN PINARLI

Histopathological effects of mesenchymal stem cells in rats with bladder and posterior urethral injuries

Background/aim: To evaluate the effects of mesenchymal stem cell (MSC) therapy in an experimental bladder and posterior urethral injury model. Materials and methods: The study subjects consisted of 40 male Wistar albino rats that were divided into four groups: control group (n = 10) (the bladder was only surgically opened and closed), sham group (n = 10) (surgical procedure), IVMSC group (n= 10) (surgical procedure and intravenous MSC treatment), and LMSC group (n = 10) (surgical procedure and local MSC treatment). Histopathological evaluation was performed for the degree of fibrosis and inflammation and the extent and intensity of staining of vascular endothelial growth factor (VEGF) and endoglin (CD105). Results: There were no significant differences between the control and LMSC groups with respect to fibrosis (P = 0.070) or inflammation (P = 0.048). Fibrosis and inflammation were significantly lower in the IVMSC (P = 0.034 for fibrosis, P = 0.080 for inflammation) and LMSC (P = 0.01 for fibrosis, P = 0.013 for inflammation) groups when compared with the sham group. No significant differences regarding fibrosis and inflammation were observed between the IVMSC and LMSC groups (P = 0.198 for fibrosis, P = 0.248 for inflammation). A significant difference was noted between the sham and LMSC groups concerning VEGF staining intensity (P = 0.017). However, no significant difference was found among the groups with regard to the extent or intensity of CD105 staining (P > 0.05). Conclusion: MSC treatment significantly decreased the development of fibrosis in a uroepithelial injury model.

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1. Pichler R, Fritsch H, Skradski V, Horninger W, Schlenck B, Rehder P, Oswald J. Diagnosis and management of pediatric urethral injuries. Urol Int 2012; 89: 136-142.
2. Delaney KM, Reddy SH, Dayama A, Stone ME Jr, Meltzer JA. Risc factors associated with bladder and urethral injuries in female children with pelvic fractures: an analysis of the National Trauma Data Bank. J Trauma Acute Care Surg 2016; 80: 472-476.
3. Aggarwal SK, Sinha SK, Kumar A, Pant N, Borkar NK, Dhua A. Traumatic structures of the posterior urethra in boys with special reference to recurrent strictures. J Pediatr Urol 2011; 7: 356-362.
4. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med 2001; 226: 507-520.
5. Ding DC, SHYU WC, Lin SZ. Mesenchymal stem cells. Cell Transplant 2011; 20: 5-14.
6. Kelahmetoglu O, Demir R, Okten G, Demir A, Alpaslan Pinarli F, Diraman E. The effect of mesenchymal stem cells and sildenafil on flap viability in perforator-based flaps for ischemia/ reperfusion injury: an experimental study. Microsurgery 2016; 36: 402-409.
7. Liu L, Chiu PW, Lam PK, Poon CC, Lam CC, Ng EK, Lai PB. Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model. Br J Surg 2015; 102: 158-168.
8. Bhansali S, Kumar V, Saikia UN, Medhi B, Jha V, Bhansali A, Dutta P. Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats. Indian J Med Res 2015; 142: 63-71.
9. Wang K, Guan Y, Liu Y, Zhu M, Li T, An D, Qu L, Che Y, Zhang G, Zhang J, Zheng XL, Kong D. Fibrin glue with autogenic bone marrow mesenchymal stem cells for urethral injury repair in rabbit model. Tissue Eng Part A 2012; 18: 2507-2517.
10. Vaegler M, Lenis AT, Daum L, Amend B, Stenzl A, Toomey P, Renninger M, Damaser MS, Sievert KD. Stem cell therapy for voiding and erectile dysfunction. Nat Rev Urol 2012; 9: 435- 447.
11. Ayyıldız A, Nuhoğlu B, Gülerkaya B. Effect of intraurethral mitomycin-C on healing and fibrosis in rats with experimentally induced urethral stricture. Int J Urol 2004; 11: 1122-1126.
12. Aydin O, Yildiz L, Kefeli M, Kandemir B. CD117 expression in normal, neoplastic, inflammatory, and reactive lesions of the thyroid. Pathol Res Pract 2008; 204: 359-365.
13. Onen A, Subası M, Arslan H, Ozen S, Basuguy E. Long-term urologic, orthopedic, and psychological outcome of posterior urethral rupture in children. Urology 2005; 66: 174-179.
14. Kucukaydin M, Ciftler AN, Guzel M, Uysal M. Management of traumatic posterior urethral injuries in children. J Pediatr Urol 2008; 4: 32.
15. Nerli RB, Koura AC, Ravish IR, Amarkhed SS, Prabha V, Alur B. Posterior urethral injury in male children: long-term follow up. J Pediatr Urol 2008; 4: 154-159.
16. Voelzke BB, Breyer BN, McAninch JW. Blunt pediatric anterior and posterior urethral trauma: 32-year experience and outcomes. J Pediatr Urol 2012; 8: 258-263.
17. Elliott DS, Barrett DM. Long-term follow-up and evaluation of primary realignment of posterior urethral disruptions. J Urol 1997; 157: 814-816.
18. Webster GD. Perineal repair of membranous urethral stricture. Urol Clin North Am 1989; 16: 303-312.
19. Mouraviev VB, Coburn M, Santucci RA. The treatment of posterior urethral disruption associated with pelvic fractures: comparative experience of early realignment versus delayed urethroplasty. J Urol 2005; 173: 873-876.
20. Singh A, Panda SS, Baipai M, Jana M, Baidya DK. Our experience, technique and long-term outcomes in the management of posterior urethral strictures. J Pediatr Urol 2014; 10: 40-44.
21. Vashishtha S, Sureka SK, Kumar J, Prabhakaran, Kapoor R, Ansari MS. Predictors for recurrence after urethroplasty in pediatric and adolescent stricture urethra. J Pediatr Surg 2014; 10: 268-273.
22. Engel O, Fisch M. Unsuccessful outcomes after posterior urethroplasty. Arab J Urol 2015; 13: 57-59.
23. Beggs KJ, Lyubimov A, Borneman JN, Bartholomew A, Moseley A, Dodds R, Archambault MP, Smith AK, McIntosh KR. Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons. Cell Transplant 2006; 15: 711-721.
24. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 2010; 5: 933-946.
25. Cambria E, Steiger J, Gunter J, Bopp A, Wolint P, Hoerstrup SP, Emmert MY. Cardiac regenerative medicine: the potential of a new generation of stem cells. Transfus Med Hemother 2016; 43: 275-281.
26. Kim JV, Lee JH, Lyoo YS, Jung DI, Park HM: The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds. Vet Dermatol 2013; 24: 242- 253.
27. Jiang H, Qu L, Li Y, Gu L, Shi Y, Zhang J, Zhu W, Li J. Bone marrow mesenchymal stem cells reduce intestinal ischemia/ reperfusion injuries in rats. J Surg Res 2011; 168: 127-134.
28. Adas G, Arıkan S, Karatepe O, Kemik O, Ayhan S, Karaöz E, Kamalı G, Eryasar B, Ustek D. Mesenchymal stem cells improve the healing of ischemic colonic anatomoses. Langenbecks Arch Surg 2011; 396: 115-126.
29. Zickri MB, Fadl SG, Metwally HG. Comparative study between intravenous and intraperitoneal stem cell therapy in amiodarone induced lung injury in rat. J Stem Cells 2014; 7: 1-11.
30. Bilen S, Pınarlı F, Ak F, Fadıllıoğlu E, Albayrak A, Boyuk G, Guler OG, Erden G. Treatment efficacy with bone marrow derived mesenchymal stem cells and minocycline in rats after cerebral ischemic injury. Stem Cell Rev 2013; 9: 219-225.
31. Horie N, Pereira MP, Niizuma K, Sun G, Keren-Gill H, Encarnacion A, Shamloo M, Hamilton SA, Jiang K, Huhn S et al. Transplated stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair. Stem Cells 2011; 29: 274-285.