Rationale for bone marrow transplantation in the treatment of autoimmune diseases.
Susumu Ikehara,Robert A. Good,Nakamura T,Kenichi Sekita,Shuji Inoue,Maung Maung Oo,Eri Muso,Katsuhiko Ogawa,Yoshihiro Hamashima +8 more
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TLDR
T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune- prone mice.Abstract:
Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.read more
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Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus
Richard K. Burt,Ann E. Traynor,Ann E. Traynor,Laisvyde Statkute,Walter G. Barr,Robert M. Rosa,James W. Schroeder,Larissa Verda,Nela Krosnjar,Kathleen Quigley,Kimberly Yaung,BS Marcello Villa,Miyuki Takahashi,Borko Jovanovic,Yu Oyama +14 more
TL;DR: In treatment-refractory SLE, autologous nonmyeloablative HSCT results in amelioration of disease activity, improvement in serologic markers, and either stabilization or reversal of organ dysfunction, providing the foundation and justification for a definitive randomized trial.
Journal ArticleDOI
Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation.
John A. Snowden,Riccardo Saccardi,Matthieu Allez,Sandro Ardizzone,Raoul Arnold,Ricard Cervera,Christopher P. Denton,Christopher J. Hawkey,Myriam Labopin,G. L. Mancardi,Roland Martin,John Moore,Jakob Passweg,Christoph Peters,Marco Rabusin,Montserrat Rovira,J.M. van Laar,Dominique Farge +17 more
TL;DR: In this paper, the authors provide revised and updated guidelines for both the current application and future development of haematopoietic SCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments.
Journal ArticleDOI
Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.
Taketoshi Kushida,Muneo Inaba,Hiroko Hisha,Naoya Ichioka,Takashi Esumi,Ryokei Ogawa,Hirokazu Iida,Susumu Ikehara +7 more
TL;DR: It is shown that a new bone marrow transplantation method consisting of fractionated irradiation, followed by intra-bone marrow (IBM) injection of whole bone marrow cells from allogeneic normal C57BL/6 (B6) mice, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants is suitable for human therapy.
Journal ArticleDOI
Autologous stem cell transplantation in the treatment of systemic sclerosis: Report from the EBMT/EULAR Registry
Dominique Farge,Jakob Passweg,J.M. van Laar,Zora Marjanovic,C. Besenthal,Jürgen Finke,Hans-Hartmut Peter,Ferdinand C. Breedveld,Willem E. Fibbe,Carol M. Black,Christopher P. Denton,I. Koetter,Francesco Locatelli,Alberto Martini,Anton Schattenberg,F.H.J. van den Hoogen,L. B. A. Van De Putte,Francesco Lanza,Renate Arnold,P. A. Bacon,Sarah J. Bingham,Fabio Ciceri,B. Didier,José Luis Díez-Martín,Paul Emery,W. Feremans,Bernd Hertenstein,Falk Hiepe,R. Luosujarvi,A. Leon Lara,Alberto M. Marmont,Angelina Martínez,H. Pascual Cascon,Chiara Bocelli-Tyndall,Eliane Gluckman,Alois Gratwohl,A Tyndall +36 more
TL;DR: It was shown that response in two thirds of the patients after HSCT was durable with an acceptable TRM and prospective, randomised trials are proceeding.
Journal ArticleDOI
Treatment of severe autoimmune disease by stem-cell transplantation
Megan Sykes,Boris Nikolic +1 more
TL;DR: The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.
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