Blog
About

1
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Mixed Bone Marrow or Mixed Stem Cell Transplantation for Prevention or Treatment of Lupus-Like Diseases in Mice

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Scientific analyses fortified by interpretations of immunodeficiency diseases as ‘experiments of nature’ have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW × BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.

          Related collections

          Most cited references 21

          • Record: found
          • Abstract: not found
          • Article: not found

          Cell migration, chimerism, and graft acceptance

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.

            Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy x 2, followed by intra-bone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy x 2 + IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donor-derived hemopoietic progenitor cells concomitantly increased. Furthermore, donor-derived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy x 2 + IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (Thy1.2(+)/B220(+)/CD4(-)/CD8(-)) disappeared. Hematolymphoid cells were reconstituted with donor-derived cells, and newly developed T cells were tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex determinants. Successful cooperation was achieved among T cells, B cells, and antigen-presenting cells when evaluated by in vitro antisheep red blood cell responses. These findings clearly indicate that this new strategy (IBM-BMT) creates the appropriate hemopoietic environment for the early recovery of hemopoiesis and donor cell engraftment, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants. This strategy would therefore be suitable for human therapy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              History of clinical transplantation.

               T Starzl (2000)
              The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations in surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipients had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts.
                Bookmark

                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2002
                2002
                09 October 2002
                : 10
                : 5-6
                : 408-420
                Affiliations
                Department of Pediatrics, University of South Florida/All Children’s Hospital, St. Petersburg, Fla., USA
                Article
                65308 Exp Nephrol 2002;10:408–420
                10.1159/000065308
                12381926
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, References: 103, Pages: 13
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/65308
                Categories
                Technical Seminar: Stem Cells in Kidney Diseases

                Comments

                Comment on this article