Volume 34, Issue 2 pp. 131-135

Tolerance Induction Through Mixed Chimerism

Toleranzinduktion durch gemischten Chimärismus

Th. Wekerle,

Th. Wekerle

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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P. Blaha,

P. Blaha

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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R. Asari,

R. Asari

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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M. Schmid,

M. Schmid

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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Ch. Kiss,

Ch. Kiss

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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E. Roth,

E. Roth

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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F. Mühlbacher,

F. Mühlbacher

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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Th. Wekerle,

Th. Wekerle

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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P. Blaha,

P. Blaha

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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R. Asari,

R. Asari

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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M. Schmid,

M. Schmid

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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Ch. Kiss,

Ch. Kiss

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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E. Roth,

E. Roth

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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F. Mühlbacher,

F. Mühlbacher

From the Division of Transplant Surgery, Department of Surgery, University of Vienna

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First published: 10 June 2002

https://doi.org/10.1046/j.1563-2563.2002.02020.x

Citations: 2

Corresponding address: Th. Wekerle, M.D., Division of Transplant Surgery, Department of Surgery, University of Vienna, Währinger Gürtel 18, A-1090 Vienna.
Fax: ++43/1/40 400 – 68 72
E-mail: [email protected]

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Abstract

Summary: Background: The induction of immunological tolerance towards the donor tissue would substantially improve outcome after organ transplantation. The establishment of mixed chimerism through the transplantation of donor bone marrow cells (BMC) is an experimental approach for tolerance induction with promising clinical potential. Permanent, robust donor-specific tolerance has been reliably achieved in various animal models of mixed chimerism. The possible toxicity of conventional bone marrow transplantation (BMT) protocols, however, has so far impeded widespread clinical application of mixed chimerism regimens.
Methods: In this article we will briefly introduce the concept of tolerance induction through mixed chimerism. We will then review recently developed mixed chimerism protocols using costimulatory blocking reagents, and will finally discuss remaining issues regarding their clinical application.
Results: In recent years new BMT protocols have been developed specifically for use in organ transplantation, which are much milder than previous ones.
Conclusions: These newly developed models of BMT with costimulatory blockade are an important step towards the clinical implementation of tolerance induction through mixed chimerism.

Abstract

Zusammenfassung: Grundlagen: Die Induktion von immunologischer Toleranz gegenüber dem Spendergewebe würde das Ergebnis nach Organtransplantationen deutlich verbessern. Die Etablierung von gemischtem Chimärismus durch die Transplantation von Spender-Knochenmarkzellen ist ein experimenteller Ansatz zur Toleranzinduktion mit vielversprechendem klinischen Potential. Dauerhafte, robuste spenderspezifische Toleranz wurde in verschiedenen Tiermodellen des gemischten Chimärismus verläßlich erreicht. Die potentielle Toxizität von konventionellen Protokollen zur Knochenmarktransplantation hat jedoch bisher die verbreitete klinische Applikation von Modellen des gemischten Chimärismus verhindert.
Methodik: In diesem Artikel stellen wir kurz das Konzept der Toleranzinduktion durch gemischten Chimärismus vor, geben einen Überblick über kürzlich entwickelte Protokolle des gemischten Chimärismus unter der Verwendung von Costimulationsblockern und diskutieren schließlich verbleibende Fragen zu deren klinischer Umsetzung.
Ergebnisse: In den letzten Jahren wurden neue Knochenmarktransplantations-Protokolle speziell für die Anwendung bei der Organtransplantation entwickelt, die viel milder als frühere sind.
Schlußfolgerungen: Diese neu entwickelten Protokolle der Knochenmarktransplantation mit Costimulationsblockade sind daher ein wichtiger Schritt näher zur klinischen Umsetzung der Toleranzinduktion durch gemischten Chimärismus.

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Volume34, Issue2

April, 2002

Pages 131-135

Tolerance Induction Through Mixed Chimerism

Toleranzinduktion durch gemischten Chimärismus

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Tolerance Induction Through Mixed Chimerism

Toleranzinduktion durch gemischten Chimärismus

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