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New Composite Tissue Allograft Model of Vascularized Bone Marrow Transplant: The Iliac Osteomyocutaneous Flap

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Abstract

Vascularized bone marrow transplant (VBMT) induces donor-specific chimerism in experimental models across the major histocompatibility barrier. An experimental model for immunotolerance studies should sustain a high antigenicity with low morbidity. Accordingly, we introduced an iliac bone osteomusculocutaneous (IBOMC) transplant model in rat. It consists of a large skin component and an abundant bone marrow cells (BMC) population. We tested this model with isograft transplantations between Lewis rats (RT1l) and with allograft transplantation between Lewis-Brown Norway (LBN RT1l + n) donors and Lewis (RT1l) recipients under low dose of cyclosporine A monotherapy. Immunologic responses were tested for donor cell engraftment and chimerism induction. All isografts survived indefinitely and allografts were viable at 200 days post-transplant under low dose of cyclosporine A. Microangiography of the graft revealed preservation of skin, muscle, and bone components. Histologic examination confirmed viability of all allograft components without signs of rejection. Long-term engraftment of donor-origin (RT1n) BMC was confirmed by donor-specific chimerism (1.2 %) in peripheral blood and bone marrow (1.65 %) compartments and by engraftment into lymphoid organs of recipients. The IBOMC transplant proved to be a reliable composite tissue allotransplantation (CTA) model. Moreover, because of its robust bone marrow component and large skin component, it is applicable to studies on immunologic responses in CTA.

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References

  1. Arslan E, Klimczak A, Siemionow M. Chimerism induction in vascularized bone marrow transplants augmented with bone marrow cells. Microsurgery. 2007;27:190.

    Article  PubMed  Google Scholar 

  2. Lee WP, Randolph MA, Weiland AJ, Yaremchuk MJ. Pro-longed survival of vascularized limb tissue allografts by donor irradiation. J Surg Res. 1995;59:578.

    Article  CAS  PubMed  Google Scholar 

  3. Lee WP, Butler PE, Randolph MA, Yaremchuk MJ. Donor modification leads to prolonged survival of limb allografts. Plast Reconstr Surg. 2001;108:1235.

    Article  CAS  PubMed  Google Scholar 

  4. Sakamoto K, Arita S, Sakamaki T, et al. Better clinical outcome in renal transplant recipients with peripheral blood microchimerism. Transplant Proc. 2000;32:1793.

    Article  CAS  PubMed  Google Scholar 

  5. Yano Y, Hara M, Miyahara T, et al. Microchimeric cells from the peripheral blood associated with cardiac grafts are bone marrow derived, long-lived and maintain acquired tolerance to minor histocompatibility antigen H-Y. Transplantation. 2001;71:1456.

    Article  CAS  PubMed  Google Scholar 

  6. Hisanaga M, Schlitt HJ, Hundrieser J, et al. Frequency and clinical correlations of allogeneic microchimerism after heart, liver, and lung transplantation. Transplant Proc. 1997;29:1215.

    Article  CAS  PubMed  Google Scholar 

  7. Elwood ET, Larsen CP, Maurer DH, et al. Microchimerism and rejection in clinical transplantation. Lancet. 1997;349:1358.

    Article  CAS  PubMed  Google Scholar 

  8. Garnier JL, Touraine JL, Gebuhrer L. No detectable microchimerism in long-term tolerant recipients of living-donor kidneys. Transplant Proc. 1997;29:1181.

    Article  CAS  PubMed  Google Scholar 

  9. Granger DK, Briedenbach WC, Pidwell DJ, Jones JW, Baxter-Lowe LA, Kaufman CL. Lack of donor hyporesponsiveness and donor chimerism after clinical transplantation of the hand. Transplantation. 2002;74:1624.

    Article  PubMed  Google Scholar 

  10. Shapiro RI, Cerra FB. A model for reimplantation and transplantation of a complex organ: the rat hind limb. J Surg Res. 1978;24:501.

    Article  CAS  PubMed  Google Scholar 

  11. Siemionow M, Ulusal BG, Ozmen S, Ulusal AE, Ozer K. Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation. Microsurgery. 2004;24:200.

    Article  PubMed  Google Scholar 

  12. Blaha P, Bigenzahn S, Koporc Z, Sykes M, Muehlbacher F, Wekerle T. Short-term immunosuppression facilitates induction of mixed chimerism and tolerance after bone marrow transplantation without cytoreductive conditioning. Transplantation. 2005;80:237.

    Article  CAS  PubMed  Google Scholar 

  13. Bigenzahn S, Blaha P, Koporc Z, et al. The role of non-deletional tolerance mechanisms in a murine model of mixed chimerism with costimulation blockade. Am J Transplant. 2005;5:1237.

    Article  CAS  PubMed  Google Scholar 

  14. Koporc Z, Pilat N, Nierlich P, et al. Murine mobilized peripheral blood stem cells have a lower capacity than bone marrow to induce mixed chimerism and tolerance. Am J Transplant. 2008;8:2025.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Barber WH, Mankin JA, Laskow DA, et al. Long-term results of a controlled prospective study with transfusion of donor-specific bone marrow in 57 cadaveric renal allograft recipients. Transplantation. 1991;51(1):70.

    Article  CAS  PubMed  Google Scholar 

  16. Ricordi C, Karatzas T, Nery J, et al. High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing. Transplantation. 1997;63:7.

    Article  CAS  PubMed  Google Scholar 

  17. Starzl TE, Demetris AJ, Murase N, Ildstad S, Ricordi C, Trucco M. Cell migration, chimerism, and graft acceptance. Lancet. 1992;339:1579.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wood K, Sachs DH. Chimerism and transplantation tolerance: cause and effect. Immunol Today. 1996;17:584; discussion 588.

    Article  CAS  PubMed  Google Scholar 

  19. Gordon CR, Tai CY, Suzuki H, et al. Review of vascularized bone marrow transplantation: current status and future clinical applications. Microsurgery. 2007;27:348.

    Article  PubMed  Google Scholar 

  20. Siemionow MZ, Izycki DM, Zielinski M. Donor-specific tolerance in fully major histocompatibility major histocompatibility complex-mismatched limb allograft transplants under an anti-alphabeta T-cell receptor monoclonal antibody and cyclosporine A protocol. Transplantation. 2003;76:1662.

    Article  CAS  PubMed  Google Scholar 

  21. Muramatsu K, Valenzuela RG, Bishop AT. Detection of chimerism following vascularized bone allotransplantation by polymerase chain reaction using a Y-chromosome specific primer. J Orthop Res. 2003;21:1056.

    Article  CAS  PubMed  Google Scholar 

  22. Klimczak A, Agaoglu G, Carnevale KA, Siemionow M. Applications of bilateral vascularized femoral bone marrow transplantation for chimerism induction across the major histocompatibility (MHC) barrier: part II. Ann Plast Surg. 2006;57:422.

    Article  CAS  PubMed  Google Scholar 

  23. Muramatsu K, Kurokawa Y, Ihara K, You-Xin S, Kawai S. Donor cell engraftment in recipient lymphoid tissues after rat limb allograft. J Surg Res. 2005;124:38.

    Article  PubMed  Google Scholar 

  24. Durham MM, Bingaman AW, Adams AB, et al. Cutting edge: administration of anti-CD40 ligand and donor bone marrow leads to hemopoietic chimerism and donor-specific tolerance without cytoreductive conditioning. J Immunol. 2000;165:1.

    Article  CAS  PubMed  Google Scholar 

  25. Wekerle T, Sykes M. Mixed chimerism as an approach for the induction of transplantation tolerance. Transplantation. 1999;68:459.

    Article  CAS  PubMed  Google Scholar 

  26. Siemionow M, Klimczak A, Unal S, Agaoglu G, Carnevale K. Hematopoietic stem cell engraftment and seeding permits multi-lymphoid chimerism in vascularized bone marrow transplants. Am J Transplant. 2008;8:1163.

    Article  CAS  PubMed  Google Scholar 

  27. Janczewska S, Ziolkowska A, Durlik M, Olszewski WL, Lukomska B. Fast lymphoid reconstitution after vascularized bone marrow transplantation in lethally irradiated rats. Transplantation. 1999;68:201.

    Article  CAS  PubMed  Google Scholar 

  28. Koguma M, Matsuda K, Okuyama R, Yanai N, Obinata M. Selective proliferation of lymphoid cells from lineage- c-Kit+ Sca-1+ cells by a clonal bone marrow stromal cell line. Exp Hematol. 1998;26:280.

    CAS  PubMed  Google Scholar 

  29. Orlic D, Girard LJ, Lee D, Anderson SM, Puck JM, Bodine DM. Interleukin-7R alpha mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors. Exp Hematol. 1997;25:217.

    CAS  PubMed  Google Scholar 

  30. Balon J, Halaburda K, Bieniaszewska M, et al. Early complete donor hematopoietic chimerism in peripheral blood indicates the risk of extensive graft-versus-host disease. Bone Marrow Transplant. 2005;35:1083.

    Article  CAS  PubMed  Google Scholar 

  31. Tai CY, Strande LF, Eydelman R, et al. Absence of graft-versus-host disease in the isolated vascularized bone marrow transplant. Transplantation. 2004;77:316.

    Article  PubMed  Google Scholar 

  32. Ozer K, Oke R, Gurunluoglu R, et al. Induction of tolerance to hind limb allografts in rats receiving cyclosporine A and antilymphocyte serum: effect of duration of the treatment. Transplantation. 2003;75:31.

    Article  CAS  PubMed  Google Scholar 

  33. Muramatsu K, Kurokawa Y, Ihara K, Sakamoto S, You-Xin S, Kawai S. Behavior of male-specific minor histocompatibility antigen in skin and limb transplantation. J Surg Res. 2003;115:106.

    Article  CAS  PubMed  Google Scholar 

  34. Hovius SE, van Adrichem LN, van der Heijden PM, Vuzevski VD, van Strik R, van der Meulen JC. Postoperative monitoring of allogeneic limb transplantation in rats. Ann Plast Surg. 1988;21:559.

    Article  CAS  PubMed  Google Scholar 

  35. Arai K, Hotokebuchi T, Miyahara H, et al. Limb allografts in rats immunosuppressed with FK506. I. Reversal of rejection and indefinite survival. Transplantation. 1989;48:782.

    Article  CAS  PubMed  Google Scholar 

  36. Santiago SF, de Faria W, Khan TF, et al. Heterotopic sternum transplant in rats: a new model of a vascularized bone marrow transplantation. Microsurgery. 1999;19:330.

    Article  CAS  PubMed  Google Scholar 

  37. Tsuchida Y, Usui M, Uede T. Vascularized bone-marrow allotransplantation in rats prolongs the survival of simultaneously grafted alloskin. J Reconstr Microsurg. 2002;18:289.

    Article  PubMed  Google Scholar 

  38. Tai CY, France MA, Strande LF, et al. An extraperitoneal isolated vascularized bone marrow transplant model in the rat. Transplantation. 2003;75:1591. a 2009 The Authors Journal compilation a 2009 European Society for Organ Transplantation.

    Article  PubMed  Google Scholar 

  39. Agaoglu G, Carnevale KA, Zins JE, Siemionow M. Bilateral vascularized femoral bone transplant: a new model of vascularized bone marrow transplantation in rats, part I. Ann Plast Surg. 2006;56:658.

    Article  CAS  PubMed  Google Scholar 

  40. Klimczak A, Unal S, Agaoglu G, Carnevale K, Siemionow M. Maintenance of donor-specific chimerism despite osteopontin-associated bone fibrosis in a vascularized bone marrow transplantation model. Plast Reconstr Surg. 2009;123:34S.

    Article  CAS  PubMed  Google Scholar 

  41. Suzuki H, Patel N, Matthews M, DelRossi AJ, Doolin EJ, Hewitt CW. Vascularized bone marrow transplantation: a new surgical approach using isolated femoral bone/bone marrow. J Surg Res. 2000;89:176.

    Article  CAS  PubMed  Google Scholar 

  42. Yonish-Rouach E, Kimchi A, Rubinstein M. The antiproliferative effect of cyclosporine on hematopoietic and lymphoblastoid cell lines–common mechanistic elements with interferon-alpha. Transplantation. 1991;51:1276.

    Article  CAS  PubMed  Google Scholar 

  43. Hirao A, Kawano Y, Takaue Y. Effects of immunosuppressants, FK506, deoxyspergualin, and cyclosporine A on immature human hematopoiesis. Blood. 1993;81:1179.

    CAS  PubMed  Google Scholar 

  44. Siemionow M, Demir Y, Mukherjee A, Klimczak A. Development and maintenance of donor-specific chimerism in semi-allogenic and fully major histocompatibility complex mismatched facial allograft transplants. Transplantation. 2005;79:558.

    Article  CAS  PubMed  Google Scholar 

  45. Nasır S, Bozkurt M, Klimczak A, Siemionow M. Large antigenic skin load in total abdominal wall transplants permits chimerism induction. Ann Plast Surg. 2008;61:572.

    Article  PubMed  Google Scholar 

  46. Nasır S, Bozkurt M, Krokowicz L, Klimczak A, Siemionow M. Correlation of chimerism with graft size and revascularization in vascularized and nonvascularized skin allografts. Ann Plast Surg. 2009;62:430.

    Article  PubMed  Google Scholar 

  47. Siemionow M, Izycki D, Ozer K, Ozmen S, Klimczak A. Role of thymus in operational tolerance induction in limb allograft transplant model. Transplantation. 2006;81:1568.

    Article  PubMed  Google Scholar 

  48. Rezzani R. Cyclosporine A, and adverse effects on organs: histochemical studies. Prog Histochem Cytochem. 2004;39:85.

    Article  CAS  PubMed  Google Scholar 

  49. Calne RY. Prope tolerance: the future of organ transplantation – from the laboratory to the clinic. Transplantation. 2004;77:930.

    Article  CAS  PubMed  Google Scholar 

  50. Adorini L, Giarratana N, Penna G. Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol. 2004;16:127.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Serdar Nasır MD .

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Nasır, S. (2015). New Composite Tissue Allograft Model of Vascularized Bone Marrow Transplant: The Iliac Osteomyocutaneous Flap. In: Siemionow, M. (eds) Plastic and Reconstructive Surgery. Springer, London. https://doi.org/10.1007/978-1-4471-6335-0_27

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  • DOI: https://doi.org/10.1007/978-1-4471-6335-0_27

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