Open Access
Bone marrow transplantation as a strategy for tolerance induction in the clinic
Ines Pree1,Nina Pilat1,Thomas Wekerle1
Divisionof Transplantation, Department of Surgery, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Austria
DOI: 10.2741/3267 Volume 14 Issue 2, pp.611-620
Published: 01 January 2009
(This article belongs to the Special Issue Transplantation: current developments and future directions)

The only way to overcome the need for life-long immunosuppression in a transplant recipient is to induce tolerance. Deletional tolerance can be reliably achieved with the induction of mixed chimerism through transplantation of donor bone marrow (BM). Despite the development of increasingly milder BM transplantation (BMT) animal models, BM engraftment in humans still requires considerably toxic conditioning and puts patients at risk for the development of GVHD. However, in a proof-of-concept trial, mixed chimerism and tolerance have been successfully induced in highly selected patients suffering from both end-stage renal disease and multiple myeloma. Meanwhile, there has been notable progress in developing advanced experimental BMT regimens, in particular through the use of costimulation blockers. Costimulation blockade in rodent models allowed the design of BMT protocols entirely devoid of irradiation. Costimulation blockers have also succeeded in more complex protocols in non-human primates. They are under clinical evaluation in renal transplantation as immunosuppressive therapy. Costimulation blockade may lead the way for the development of milder BMT protocols and broader application of mixed chimerism in organ transplantation.

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Ines Pree, Nina Pilat, Thomas Wekerle. Bone marrow transplantation as a strategy for tolerance induction in the clinic. Frontiers in Bioscience-Landmark. 2009. 14(2); 611-620.