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Mixed chimerism through donor bone marrow transplantation: a tolerogenic cell therapy for application in organ transplantation

Pilat, Nina; Hock, Karin; Wekerle, Thomas

Current Opinion in Organ Transplantation: February 2012 - Volume 17 - Issue 1 - p 63–70
doi: 10.1097/MOT.0b013e32834ee68b
STEM CELL TRANSPLANTATION: Edited by Marc H. Dahlke
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Purpose of review Organ transplantation is the state-of-the-art treatment for end-stage organ failure; however, long-term graft survival is still unsatisfactory. Despite improved immunosuppressive drug therapy, patients are faced with substantial side effects and the risk of chronic rejection with subsequent graft loss. The transplantation of donor bone marrow for the induction of mixed chimerism has been recognized to induce donor-specific tolerance a long time ago, but safety concerns regarding toxicities of current bone marrow transplantation (BMT) protocols impede widespread application.

Recent findings Recent studies in nonhuman primates and kidney transplant patients have demonstrated successful induction of allograft tolerance even though – in contrast to murine models – only transient chimerism was achieved. Progress toward the development of nontoxic murine BMT protocols revealed that Treg therapy is a potent therapeutic adjunct eliminating the need for cytotoxic recipient conditioning. Furthermore, new insight into the mechanisms underlying tolerization of CD4 and CD8 T cells in mixed chimeras has been gained and has identified possible difficulties impeding clinical translation.

Summary This review will address the recent advances in murine models as well as findings from the first clinical trials for the induction of tolerance through mixed chimerism. Both the potential for more widespread clinical application and the remaining hurdles and challenges of this tolerance approach will be discussed.

Division of Transplantation, Department of Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

Correspondence to Thomas Wekerle, MD, Division of Transplantation, Department of Surgery, Vienna General Hospital, Waehringer Guertel 18, 1090 Vienna, Austria. Tel: +43 1 40400 5621; fax: +43 1 40400 6872; e-mail: Thomas.Wekerle@meduniwien.ac.at

© 2012 Lippincott Williams & Wilkins, Inc.