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Experimental Models of Penile and Lower Limb Transplantation: Are They Really Translational?

  • Yalcin Kulahci
  • Huseyin Karagoz
  • Fatih Zor
Vascularized Composite Allografts (V Gorantla and R Barth, Section Editors)
  • 9 Downloads
Part of the following topical collections:
  1. Topical Collection on Vascularized Composite Allografts

Abstract

Purpose of Review

The purpose of this review is to evaluate the recent literature about animal models for penile and lower limb transplantation, regarding their relevance to the clinical scenario.

Recent Findings

Although both penile and lower limb transplantations have been sharing same problems with all other vascularized composite allotransplantations, they have their unique issues that need to be addressed. There is no appropriate animal model to demonstrate functions of both penile and lower limb transplantation.

Summary

We reevaluate and underline the interesting and important findings of the certain animal models of the penile and lower limb transplantation. Current and future clinical applicability and feasibility have also been discussed.

Keywords

Experimental model Vascularized composite allotransplantation Penile transplantation Lower extremity transplantation 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Dubernard JM, Owen E, Herzberg G, Lanzetta M, Martin X, Kapila H, et al. Human hand allograft: report on first 6 months. Lancet. 1999;353(9161):1315–20.CrossRefGoogle Scholar
  2. 2.
    • Sopko NA, Tuffaha SH, Lough D, Brandacher G, WPA L, Bivalacqua TJ, et al. Penile Allotransplantation for complex genitourinary reconstruction. J Urol. 2017;198(2):274–80 Comprehensive review for the penile transplant cases as well as penile transplant indications, preclinical models, and immunosuppression therapy.CrossRefGoogle Scholar
  3. 3.
    Hu W, Lu J, Zhang L, Wu W, Nie H, Zhu Y, et al. A preliminary report of penile transplantation. Eur Urol. 2006;50(4):851–3.CrossRefGoogle Scholar
  4. 4.
    Bateman C. World’s first successful penis transplant at Tygerberg Hospital. S Afr Med J. 2015;105(4):251–2.CrossRefGoogle Scholar
  5. 5.
    •• Merwe AV, Zarrabi A, Zuhlke A, Barsdorf N, Moosa R. Lessons learned from the world’s first successful penis allotransplantation. J Mater Sci Mater Med. 2017;28(2):27 Points out the difficulties about management of pre- and postsurgical evaluations for penile transplantation.CrossRefGoogle Scholar
  6. 6.
    •• van der Merwe A, Graewe F, Zuhlke A, Barsdorf NW, Zarrabi AD, Viljoen JT, et al. Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up. Lancet. 2017;390(10099):1038–47 This is the first clinical report of penile allotransplantation.CrossRefGoogle Scholar
  7. 7.
    Cetrulo CL, Jr., Li K, Salinas HM, Treiser MD, Schol I, Barrisford GW, et al. Penis transplantation: first US experience. Ann Surg. 2017.Google Scholar
  8. 8.
    Hoebeke P. Re: Weilie Hu, Jun Lu, Lichao Zhang, et al. A preliminary report of penile transplantation. Eur urol 2006;50:851–3. Eur Urol. 2007;51(4):1146–7.Google Scholar
  9. 9.
    Cooney DS, Tuffaha SH, Cooney CM, Brandacher G, Lee WPA, Redett RJ. Reconstructive transplantation for penile restoration. Vascularized Composite Allotransplantation. 2015;2(4):61–4.CrossRefGoogle Scholar
  10. 10.
    •• Zuker RM, Redett R, Alman B, Coles JG, Timoney N, Ein SH. First successful lower-extremity transplantation: technique and functional result. J Reconstr Microsurg. 2006;22(4):239–44 This is the first clinical report of lower extremity allotransplantation.CrossRefGoogle Scholar
  11. 11.
    Fattah A, Cypel T, Donner EJ, Wang F, Alman BA, Zuker RM. The first successful lower extremity transplantation: 6-year follow-up and implications for cortical plasticity. Am J Transplant. 2011;11(12):2762–7.CrossRefGoogle Scholar
  12. 12.
    de Lago M. World’s first double leg transplantation is carried out in Spain. BMJ. 2011;343:d4541.CrossRefGoogle Scholar
  13. 13.
    Cavadas PC, Thione A, Carballeira A, Blanes M. Bilateral transfemoral lower extremity transplantation: result at 1 year. Am J Transplant. 2013;13(5):1343–9.CrossRefGoogle Scholar
  14. 14.
    •• Gorantla VS, Zor F, Nasir S, Breidenbach WC, Davis MR. Lower extremity transplantation: concepts, challenges, and controversies. In: Tepe V, Peterson C, editors. Full Stride. New York: Springer; 2017. p. 195–212. Explains clearly preoperative and postoperative challenges of lower extremity transplantations.CrossRefGoogle Scholar
  15. 15.
    Nasir S, Kilic YA, Karaaltin MV, Erdem Y. Lessons learned from the first quadruple extremity transplantation in the world. Ann Plast Surg. 2014;73(3):336–40.PubMedGoogle Scholar
  16. 16.
    Landin L, Dominguez A, Sanchez-Sanchez M. Discussion of lessons learned from the first quadruple extremity transplantation in the world: the logic of massive allograft transplantation. Ann Plast Surg. 2014;73(3):341–2.CrossRefGoogle Scholar
  17. 17.
    Swanson EW, Cheng HT, Lough DM, Lee WPA, Shores J, Brandacher G. Lower extremity allotransplantation: are we ready for prime time? Vascularized Composite Allotransplantation. 2015;2(2):37–46.CrossRefGoogle Scholar
  18. 18.
    Swanson EW, Brandacher G, Gordon CR. Discussion of lessons learned from the first quadruple extremity transplantation in the world: comments and concerns regarding quadruple extremity allotransplantation. Ann Plast Surg. 2014;73(3):343–5.CrossRefGoogle Scholar
  19. 19.
    Bozkurt M, Klimczak A, Nasir S, Zor F, Krokowicz L, Siemionow M. Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation. Microsurgery. 2013;33(1):43–50.CrossRefGoogle Scholar
  20. 20.
    Kulahci Y, Altuntas SH, Karagoz H, Cwykiel JM, Zor F, Siemionow M. A new total hemiface allotransplantation model in rats. Microsurgery. 2016;36(3):230–8.CrossRefGoogle Scholar
  21. 21.
    Siemionow M, Kulahci Y. Experimental models of composite tissue allograft transplants. Semin Plast Surg. 2007;21(4):205–12.CrossRefGoogle Scholar
  22. 22.
    Siemionow M, Kulahci Y. Facial transplantation. Semin Plast Surg. 2007;21(4):259–68.CrossRefGoogle Scholar
  23. 23.
    Kulahci Y, Bayram Y, Karagoz H, Sever C, Sahin C. Experimental craniofacial composite tissue allotransplantation (CCTA) models in rats. Arch Clin Exp Surg. 2012;1(3):181–7.CrossRefGoogle Scholar
  24. 24.
    Kulahci Y, Klimczak A, Madajka M, Altuntas S, Siemionow M. Long-term survival of composite hemiface/mandible/tongue allografts correlates with multilineage chimerism development in the lymphoid and myeloid compartments of recipients. Transplantation. 2010;90(8):843–52.CrossRefGoogle Scholar
  25. 25.
    Akyurek M, Ozkan O, Safak T, Ozgentas HE, Dunn RM. The penile flap in the rat: description and autotransplantation. Ann Plast Surg. 2005;55(1):94–100 discussion 1.CrossRefGoogle Scholar
  26. 26.
    Karamursel S, Karamursel T, Celebioglu S. Rat penis as a replantation model. Ann Plast Surg. 2005;55(5):503–7.CrossRefGoogle Scholar
  27. 27.
    Seyam RM, Kattan SA, Assad LW, El-Sayed RM, Almohanna FH. Penile autotransplantation in rats: an animal model. Urol Ann. 2013;5(4):255–8.CrossRefGoogle Scholar
  28. 28.
    Koga H, Yamataka A, Wang K, Kato Y, Lane GJ, Kobayashi H, et al. Experimental allogenic penile transplantation. J Pediatr Surg. 2003;38(12):1802–5.CrossRefGoogle Scholar
  29. 29.
    Sonmez E, Nasir S, Siemionow M. Penis allotransplantation model in the rat. Ann Plast Surg. 2009;62(3):304–10.CrossRefGoogle Scholar
  30. 30.
    Zhao Y, Hu W, Zhang L, Guo F, Wang W, Wang B, et al. Penis Allotransplantation in beagle dog. Biomed Res Int. 2016;2016:1489204.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Kapoor MS, Khan SA, Gupta SK, Choudhary R, Bodakhe SH. Animal models of erectile dysfunction. J Pharmacol Toxicol Methods. 2015;76:43–54.CrossRefGoogle Scholar
  32. 32.
    Shapiro RI, Cerra FB. A model for reimplantation and transplantation of a complex organ: the rat hind limb. J Surg Res. 1978;24(6):501–6.CrossRefGoogle Scholar
  33. 33.
    Lipson RA, Kawano H, Halloran PF, McKee NH, Pritzker KP, Langer F. Vascularized limb transplantation in the rat. I. Results with syngeneic grafts. Transplantation. 1983;35(4):293–9.CrossRefGoogle Scholar
  34. 34.
    Lipson RA, Kawano H, Halloran PF, Pritzker KP, Kandel R, Langer F. Vascularized limb transplantation in the rat. II. Results with allogeneic grafts. Transplantation. 1983;35(4):300–4.CrossRefGoogle Scholar
  35. 35.
    Ulusal AE, Ulusal BG, Hung LM, Wei FC. Heterotopic hindlimb allotransplantation in rats: an alternative model for immunological research in composite-tissue allotransplantation. Microsurgery. 2005;25(5):410–4.CrossRefGoogle Scholar
  36. 36.
    Ozer K. Rat hind limb and cremaster allograft transplantation model. In: Siemionow MZ, editor. Plastic and reconstructive surgery. London: Springer; 2015. p. 161–5.Google Scholar
  37. 37.
    Muramatsu K, Moriya A, Hashimoto T, Taguchi T. Immunomodulatory effects of pre-irradiated extremity allograft in the rodent model. J Plast Reconstr Aesthet Surg. 2012;65(7):950–5.CrossRefGoogle Scholar
  38. 38.
    Muramatsu K, Kato H, Yoshida Y, Moriya A, Taguchi T. Myeloablative irradiation and granulocyte colony-stimulating factor prolong the survival of chimeric limb allografts in a rodent model. Plast Reconstr Surg. 2010;126(1):53–60.CrossRefGoogle Scholar
  39. 39.
    Lee WP, Butler PE, Randolph MA, Yaremchuk MJ. Donor modification leads to prolonged survival of limb allografts. Plast Reconstr Surg. 2001;108(5):1235–41.CrossRefGoogle Scholar
  40. 40.
    Lee WP, Randolph MA, Weiland AJ, Yaremchuk MJ. Prolonged survival of vascularized limb tissue allografts by donor irradiation. J Surg Res. 1995;59(5):578–88.CrossRefGoogle Scholar
  41. 41.
    Fries CA, Villamaria CY, Spencer JR, Rickard RF, Gorantla VS, Davis MR. A porcine orthotopic forelimb vascularized composite allotransplantation model: technical considerations and translational implications. Plast Reconstr Surg. 2016;138(3):461e–71e.CrossRefGoogle Scholar
  42. 42.
    Ozer K, Adanali G, Zins J, Siemionow M. In vivo microscopic assessment of cremasteric microcirculation during hindlimb allograft rejection in rats. Plast Reconstr Surg. 1999;103(7):1949–56.CrossRefGoogle Scholar
  43. 43.
    Siemionow M, Ozer K, Porvasnik S, Zins J. Microcirculatory window for early detection of allograft rejection. Ann Plast Surg. 2000;44(6):637–43.CrossRefGoogle Scholar
  44. 44.
    Ozer K, Siemionow M. Combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibody therapy prolongs allograft survival in rat hind-limb transplants. J Reconstr Microsurg. 2001;17(7):511–7 discussion 8.CrossRefGoogle Scholar
  45. 45.
    Gorantla VS, Prabhune KA, Perez-Abadia G, Ildstad ST, Maldonado C, Orhun HI, et al. Composite tissue allotransplantation in chimeric hosts: part I. prevention of graft-versus-host disease. Transplantation. 2003;75(7):922–32.CrossRefGoogle Scholar
  46. 46.
    Mundinger GS, Drachenberg CB. Chronic rejection in vascularized composite allografts. Curr Opin Organ Transplant. 2014;19(3):309–14.CrossRefGoogle Scholar
  47. 47.
    Kaufman CL, Ouseph R, Blair B, Kutz JE, Tsai TM, Scheker LR, et al. Graft vasculopathy in clinical hand transplantation. Am J Transplant. 2012;12(4):1004–16.CrossRefGoogle Scholar
  48. 48.
    Gordon CR, Zor F, Cetrulo C Jr, Brandacher G, Sacks J, Lee WP. Concomitant face and hand transplantation: perfect solution or perfect storm? Ann Plast Surg. 2011;67(3):309–14.CrossRefGoogle Scholar
  49. 49.
    Khalil AA, Aziz FA, Hall JC. Reperfusion injury. Plast Reconstr Surg. 2006;117(3):1024–33.CrossRefGoogle Scholar
  50. 50.
    Faroni A, Mobasseri SA, Kingham PJ, Reid AJ. Peripheral nerve regeneration: experimental strategies and future perspectives. Adv Drug Deliv Rev. 2015;82-83:160–7.CrossRefGoogle Scholar
  51. 51.
    Midha R. Peripheral nerve regeneration and nerve repair. In: Binder MD, Hirokawa N, editors. Encyclopedia of neuroscience. Berlin: Springer; 2009. p. 3124–8.CrossRefGoogle Scholar
  52. 52.
    Hautz T, Wolfram D, Grahammer J, Starzl R, Krapf C, Pratschke J, et al. Mechanisms and mediators of inflammation: potential models for skin rejection and targeted therapy in vascularized composite allotransplantation. Clin Dev Immunol. 2012;2012:757310.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Plastic, Reconstructive and Aesthetic Surgeon and Hand Surgeon, Little LabUniversity of PittsburghPittsburghUSA
  2. 2.Plastic, Reconstructive and Aesthetic SurgeonWake Forest Institute for Regenerative MedicineWinston-SalemUSA

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