Tzu Chi Medical Journal
Volume 20, Issue 2 , Pages 101-108, June 2008

Induction of Tolerance Through Mixed Chimerism for Composite Tissue Allotransplantation: Insights, Problems and Solutions

  • Wei-Chao Huang

      Affiliations

    • Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
    • Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Chiayi, Taiwan
    • ,
  • Jeng-Yee Lin

      Affiliations

    • Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
    • Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
    • ,
  • Fu-Chan Wei

      Affiliations

    • Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
    • ,
  • Shuen-Kuei Liao

      Affiliations

    • Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
    • Corresponding Author InformationCorresponding author. Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259, Wen-Hua 1st Road, Kweishan, Taoyuan, Taiwan

Received 21 September 2007; received in revised form 2 October 2007; accepted 31 October 2007.

Article Outline

Abstract 

Composite tissue allotransplantation (CTA) research faces two critical challenges. Firstly, the most applicable experimental model(s) in which CTA tolerance induction regimens should be characterized and tested requires clarification. Secondly, it has not been determined what would constitute a suitable endpoint for clinical trials of such methodologies before progression toward wider clinical application could be considered appropriate. Currently, the most reliable method to induce CTA tolerance in animals is to establish mixed hematopoietic chimerism using bone marrow transplantation (BMT) from an allogeneic donor. This approach has three important constraints: (i) the requirement for toxic myeloablative conditioning; (ii) a prerequisite 28-day delay period between BMT and CTA; and (iii) the potential for inducing graft-versus-host disease (GVHD). We review the history of chimerism induction for CTA, the strategies that have been proposed to circumvent CTA-related problems, and the insights that have been gained from our own research into these issues. The benefits of vascularized BMT (VBMT) over conventional BMT for inducing CTA tolerance are highlighted. The establishment of mixed chimerism and the induction of tolerance require further research and refinement before they can be applied clinically. A safe and robust method of tolerance induction encourages wider application of reconstructive CTA with fewer ethical obstacles.

Keywords:  Composite tissue allotransplantation , Hematopoietic stem cells , Mixed chimerism , Tolerance , Transplantation

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PII: S1016-3190(08)60018-X

doi:10.1016/S1016-3190(08)60018-X

Tzu Chi Medical Journal
Volume 20, Issue 2 , Pages 101-108, June 2008

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