Skip to main content

Cellular Therapies in Vascularized Composite Allograft

  • Chapter
  • First Online:
Plastic and Reconstructive Surgery

Abstract

The preclinical experimental models of donor bone marrow transplantation (BMT) for chimerism induction have rapidly developed in the past years. The presence of mixed chimerism in solid organs and in vascularized composite allograft (VCA) transplantations is on focus as tolerance-inducing strategy for allograft survival with minimal or without long-lasting immunosuppression allowing for widespread application in the clinic. In this Chapter we summarize our experience of cellular therapies with donor hematopoietic cells for chimerism induction in VCA. We introduce different alternative methods of bone marrow cell (BMC) delivery including: (1) standard intravenous, (2) intraosseous, and into immunoprivileged compartments (3) under kidney capsule, (4) into testis, and (5) intrathecal infusion, for chimerism induction. The efficacy of donor BMT for chimerism induction was tested on limb, vascularised skin and face transplant experimental models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BMC:

Bone marrow cells

BMT:

Bone marrow transplantation

CsA:

Cyclosporine A

GvHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cells transplantation

LBN:

Lewis-Brown Norway

mAb:

Monoclonal antibody

MACS:

Magnetic assay cell sorting

MHC:

Major histocompatibility complex

VCA:

Vascularized composite allografts

αβ-TCR:

αβ- T-cell receptor

References

  1. Pilat N, Hock K, Wekerle T. Mixed chimerism through donor bone marrow transplantation: a tolerogenic cell therapy for application in organ transplantation. Curr Opin Organ Transplant. 2012;17:63–70.

    Article  CAS  PubMed  Google Scholar 

  2. Leonard DA, McGrouther DA, Kurtz JM, Cetrulo Jr CL. Tolerance induction strategies in vascularized composite allotransplantation: mixed chimerism and novel developments. Clin Dev Immunol. 2012;2012:863264.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Siemionow M, Klimczak A. Advances in the development of experimental composite tissue transplantation models. Transpl Int. 2010;23:2–13.

    Article  PubMed  Google Scholar 

  4. Siemionow M, Ozer K, Izycki D, Unsal M, Klimczak A. A new method of bone marrow transplantation leads to extension of skin allograft survival. Transplant Proc. 2005;37:2309–14.

    Article  CAS  PubMed  Google Scholar 

  5. Siemionow M, Zielinski M, Ozmen S, Izycki D. Intraosseous transplantation of donor-derived hematopoietic stem and progenitor cells induces donor-specific chimerism and extends composite tissue allograft survival. Transplant Proc. 2005;37:2303–8.

    Article  CAS  PubMed  Google Scholar 

  6. Siemionow MZ, Klimczak A, Unal S. Different routes of donor-derived hematopoietic stem cell transplantation for donor-specific chimerism induction across MHC barrier. Transplant Proc. 2005;37:62–4.

    Article  CAS  PubMed  Google Scholar 

  7. Klimczak A, Unal S, Jankowska A, Coburn C, Siemionow M. Donor-origin cell engraftment after intraosseous or intravenous bone marrow transplantation in a rat model. Bone Marrow Transplant. 2007;40:373–80.

    Article  CAS  PubMed  Google Scholar 

  8. Siemionow M, Klimczak A. Chimerism-based experimental models for tolerance induction in vascularized composite allografts: Cleveland clinic research experience. Clin Dev Immunol. 2013;2013:831410.

    Article  PubMed Central  PubMed  Google Scholar 

  9. 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;8:1163–76.

    Article  CAS  PubMed  Google Scholar 

  10. Cashman JD, Eaves CJ. High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID mice. Blood. 2000;96:3979–81.

    CAS  PubMed  Google Scholar 

  11. Castello S, Podesta M, Menditto VG, et al. Intra-bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency. Exp Hematol. 2004;32:782–7.

    Article  PubMed  Google Scholar 

  12. Saglio F, Berger M, Vassallo E, et al. Intrabone cord blood hematopoietic stem cell transplantation in a subset of very high-risk pediatric patients: a safety and feasibility pilot study. J Pediatr Hematol Oncol. 2012;34:359–63.

    Article  PubMed  Google Scholar 

  13. Frassoni F, Gualandi F, Podesta M, et al. Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. Lancet Oncol. 2008;9:831–9.

    Article  CAS  PubMed  Google Scholar 

  14. Wang J, Kimura T, Asada R, et al. SCID-repopulating cell activity of human cord blood-derived CD34- cells assured by intra-bone marrow injection. Blood. 2003;101:2924–31.

    Article  CAS  PubMed  Google Scholar 

  15. Esumi T, Inaba M, Ichioka N, Kushida T, Iida H, Ikehara S. Successful allogeneic leg transplantation in rats in conjunction with intra-bone marrow injection of donor bone marrow cells. Transplantation. 2003;76:1543–8.

    Article  CAS  PubMed  Google Scholar 

  16. Ikehara S. A novel strategy for allogeneic stem cell transplantation: perfusion method plus intra-bone marrow injection of stem cells. Exp Hematol. 2003;31:1142–6.

    Article  PubMed  Google Scholar 

  17. Carrancio S, Romo C, Ramos T, et al. Effects of MSC coadministration and route of delivery on cord blood hematopoietic stem cell engraftment. Cell Transplant. 2013;22:1171–83.

    Article  CAS  PubMed  Google Scholar 

  18. Siemionow M, Klimczak A. Immunodepletive anti-alpha/beta-TCR antibody in transplantation of composite tissue allografts: Cleveland clinic research experience. Immunotherapy. 2009;1:585–98.

    CAS  PubMed  Google Scholar 

  19. 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;79:558–67.

    Article  CAS  PubMed  Google Scholar 

  20. Yazici I, Unal S, Siemionow M. Composite hemiface/calvaria transplantation model in rats. Plast Reconstr Surg. 2006;118:1321–7.

    Article  CAS  PubMed  Google Scholar 

  21. 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;90:843–52.

    Article  CAS  PubMed  Google Scholar 

  22. Burgos FJ, Gomez V, Pascual J, et al. Pancreas islet transplantation in the genitourinary tract associated with renal transplantation: an experimental study. Transplant Proc. 2006;38:2585–7.

    Article  CAS  PubMed  Google Scholar 

  23. Fijak M, Bhushan S, Meinhardt A. Immunoprivileged sites: the testis. Methods Mol Biol. 2011;677:459–70.

    Article  CAS  PubMed  Google Scholar 

  24. Zhu B, Luo L, Chen Y, Paty DW, Cynader MS. Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis. J Immunol. 2002;169:1561–9.

    Article  CAS  PubMed  Google Scholar 

  25. Jundzill A, Klimczak A, Sonmez E, Gatherwright J, Siemionow M. Prolongation of composite tissue allograft survival using alternative routes of bone marrow transplantation. Transpl Int. 2009;22:9–10.

    Google Scholar 

  26. Jundzill A, Klimczak A, Brzezicki G, Gatherwright J, Sonmez E, Siemionow M. Effect of chimerism induction after bone marrow transplantation into different anatomical compartments. Am J Transpl. 2009;9(Suppl 2):466.

    Google Scholar 

  27. Hunig T, Wallny HJ, Hartley JK, Lawetzky A, Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989;169:73–86.

    Article  CAS  PubMed  Google Scholar 

  28. Waid TH, Lucas BA, Amlot P, et al. T10B9.1A-31 anti-T-cell monoclonal antibody: preclinical studies and clinical treatment of solid organ allograft rejection. Am J Kidney Dis. 1989;14:61–70.

    Article  CAS  PubMed  Google Scholar 

  29. Waid TH, Thompson JS, Siemionow M, Brown SA. T10B9 monoclonal antibody: a short-acting nonstimulating monoclonal antibody that spares gammadelta T-cells and treats and prevents cellular rejection. Drug Des Dev Ther. 2009;3:205–12.

    Article  Google Scholar 

  30. Nakamura K, Inaba M, Sugiura K, et al. Enhancement of allogeneic hematopoietic stem cell engraftment and prevention of GVHD by intra-bone marrow bone marrow transplantation plus donor lymphocyte infusion. Stem Cells. 2004;22:125–34.

    Article  PubMed  Google Scholar 

  31. Miyake T, Inaba M, Fukui J, et al. Prevention of graft-versus-host disease by intrabone marrow injection of donor T cells: involvement of bone marrow stromal cells. Clin Exp Immunol. 2008;152:153–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Locatelli F. Improving cord blood transplantation in children. Br J Haematol. 2009;147:217–26.

    Article  PubMed  Google Scholar 

  33. Siemionow M, Izycki D, Ozer K, Ozmen S, Klimczak A. Role of thymus in operational tolerance induction in limb allograft transplant model. Transplantation. 2006;81:1568–76.

    Article  PubMed  Google Scholar 

  34. Devauchelle B, Badet L, Lengele B, et al. First human face allograft: early report. Lancet. 2006;368:203–9.

    Article  PubMed  Google Scholar 

  35. Schneeberger S, Gorantla VS, Brandacher G, et al. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013;257:345–51.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aleksandra Klimczak PhD, DSc .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Klimczak, A., Jundzill, A. (2015). Cellular Therapies in Vascularized Composite Allograft. In: Siemionow, M. (eds) Plastic and Reconstructive Surgery. Springer, London. https://doi.org/10.1007/978-1-4471-6335-0_74

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-6335-0_74

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-6334-3

  • Online ISBN: 978-1-4471-6335-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics