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The Science of Reconstructive Transplantation pp 227–254Cite as

Bone Marrow-Derived Ex Vivo Created Hematopoietic Chimeric Cells to Support Engraftment and Maintain Long-Term Graft Survival in Reconstructive Transplantation

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Vascularized composite allotransplantation (VCA) introduces a promising alternative approach to standard reconstructive procedures for severely disfigured patients. Currently, VCA research is focusing on the development of immunomodulatory protocols for tolerance induction. The ultimate goal is to reduce or preferably eliminate the need for toxic, lifelong immunosuppression and to prevent both acute and chronic rejection.

Currently, the most successful approaches for tolerance induction are chimerism-based protocols using cellular therapies. Chimerism originated in the early 1950s from work on small animal models and opened a new approach for tolerance induction that allowed for transition from the laboratory to the first clinical trials.

Siemionow’s group at Cleveland Clinic, based on their experience in developing multiple immunosuppressive protocols in VCA models, created a new bone marrow derived, ex vivo fused, donor–recipient chimeric cell therapy and tested its efficacy in VCA models.

This innovative chimeric cell therapy, combined with a short-term selective immunomodulatory protocol, prolonged VCA survival. This chapter describes a series of studies that led to the development and creation of chimeric cells, and it also presents the potential benefits of chimeric cell protocols. Successful application of chimeric cell protocol in VCA experimental models will advance the field of reconstructive transplantation toward clinical trials.

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Abbreviations

ACI:

August Copenhagen Irish (An inbred rat strain derived by breeding an August male with an Irish coat and a Copenhagen 2331 female)

Anti-αβTCR monoclonal antibody:

Anti-αβ T cell receptor monoclonal antibody

BMCs:

Bone marrow cells

BMT:

Bone marrow transplantation

CsA:

Cyclosporine A

CTL:

cytotoxic T lymphocytes

GVHD:

Graft-versus-host disease

Gy:

Gray (radiation unit)

HLA:

Human leukocyte antigen

LBN:

Lewis Brown Norway (An inbred rat strain derived by breeding a Brown Norway male and a Lewis female)mAb monoclonal antibodies

MHC:

Major histocompatibility complex

MLR:

Mixed lymphocyte reaction

NK:

Natural killer cells

TBI:

Total body irradiation

T-reg:

Regulatory T cells

VCA:

Vascularized composite allotransplantation

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Authors and Affiliations

  1. Department of Orthopaedics, University of Illinois at Chicago, 900 S Ashland Ave, Room 3356 MBRB, 60607, Chicago, IL, USA

    Maria Siemionow MD, PhD, DSc & Joanna Cwykiel MSc

  2. Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH, USA

    Maria Madajka PhD

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  1. Maria Siemionow MD, PhD, DSc
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  2. Joanna Cwykiel MSc
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  3. Maria Madajka PhD
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Correspondence to Maria Siemionow MD, PhD, DSc .

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Editors and Affiliations

  1. Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Gerald Brandacher

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Siemionow, M., Cwykiel, J., Madajka, M. (2015). Bone Marrow-Derived Ex Vivo Created Hematopoietic Chimeric Cells to Support Engraftment and Maintain Long-Term Graft Survival in Reconstructive Transplantation. In: Brandacher, G. (eds) The Science of Reconstructive Transplantation. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2071-6_16

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