We have previously found that a major histocompatibility complex (MHC) restriction exists between pluripotent hemopoietic stem cells (P-HSCs) and stromal cells. Based on this finding, we have recently found using chimerism-resistant mouse combinations that successful allogeneic (allo) BMT can be executed by recruiting donor bone marrow stromal cells. The strategies include donor bone grafts under the skin, injection of whole bone marrow cells (BMCs) including stromal cells via the portal vein (PV), and injection of whole BMCs directly into the bone marrow cavity (intra-bone marrow [IBM] injection). In this paper, we show how stromal cells play crucial roles in overcoming chimerism-resistant allo BMT.

Keywords:
Allogeneic bone marrow transplantation, Autoimmune diseases, Stromal cells, Portal venous injection, Intra-bone marrow injection
1.
Ikehara S, Good RA, Nakamura T, Sekita K, Inoue S, Maung Maung OO, Ouso E, Ogawa K, Hamashima Y: Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA 1985;82:2483–2487.
2.
Ikehara S, Ohtsuki H, Good RA, Asamoto H, Nakamura T, Sekita K, Muso E, Tochino Y, Ida T, Kuzuya H, Imura H, Hamashima Y: Prevention of type I diabetes in nonobese diabetic mice by allogeneic bone marrow transplantation. Proc Natl Acad Sci USA 1985;82:7743–7747.
3.
Yasumizu R, Sugiura K, Iwai H, Inaba M, Nakino S, Ida T, Imura H, Hamashima Y, Good RA, Ikehara S: Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue. Proc Natl Acad Sci USA 1987;84:6555–6557.
4.
Oyaizu N, Yasumizu R, Inaba-Miyama M, Nomura S, Yoshida H, Miyawaki S, Shibata Y, Mitsuoka S, Yasunaga K, Morii S, Good RA, Ikehara S: (NZW × BXSB)F1 mouse: A new model of idiopathic thrombocytopenic purpura. J Exp Med 1988;167:2017–2022.
5.
Ikehara S, Yasumizu R, Inaba M, izui S, Hayakawa K, Sekita K, Toki J, Sugiura K, Iwai H, Nakamura T, Muso E, Hamashima Y, Good RA: Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation. Proc Natl Acad Sci USA 1989;86:3306–3310.
6.
Adachi Y, Inaba M, Amoh Y, Yoshifusa H, Nakamura Y, Suzuki H, Akamatsu S, Nakai S, Haruna H, Adachi M, Ikehara S: Effects of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. Immunobiology 1995;192:218–230.
7.
Soe Than, Ishida H, Inaba M Fukuba Y, Seino Y, Adachi M, Imura H, Ikehara S: Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice. J Exp Med 1992;176:12331238.
8.
Nishimura M, Toki J, Sugiura K, Hashimoto F, Tomita T, Fujishima H, Hiramatsu Y, Nishioka N, Nagata N, Takahashi Y, Ikehara S: Focal glomerulonephritis is a stem cell disorder. J Exp Med 1994;179;1053–1058.
9.
Ikehara S, Kawamura M, Takao F, Inaba M, Yasumizu R, Soe Than, Hisha H, Sugiura K, Koide Y, Yoshida TO, Ida T, Imura H, Good RA: Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Proc Natl Acad Sci USA 1990;87:8341–834.
10.
Kawamura M, Hisha H, Li Y, Fukuhara S, Ikehara S: Distinct qualitative differences between normal and abnormal hemopoietic stem cells in vivo and in vitro. Stem Cells 1997;15:56–62.
11.
Hashimoto F, Sugiura K, Inoue K, Ikehara S: Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vivo. Blood 1997;89:49–54.
12.
Sugiura K, Hisha H, Ishikawa J, Adachi Y, Taketani S, Lee S, Nagahama T, Ikehara S: Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vitro. Stem Cells, in press.
13.
Izumi-Hisha H, Soe Than, Ogata H, Inaba M, Ikehara S, Kawai M: Monoclonal antibodies against a preadipose cell line (MC3T3-G2/PA6) which can support hemopoiesis. Hybridoma 1991;10:103–112.
14.
Cherry, Yasumizu R, Toki J, Asou H, Nishino T, Komatsu Y, Ikehara S: Production of hemopoietic stem cell-chemotactic factor by bone marrow stromal cells. Blood 1994;83:964–971.
15.
Takeuchi K, Inaba M, Miyashima S, Ogawa R, Ikehara S: A new strategy for treatment of autoimmune diseases in chimeric resistant MRL/lpr mice. Blood 1998;91:4616–4623.
16.
Zhang Y, Yasumizu R, Sugiura K, Hashimoto F, Amoh Y, Lian Z, Cherry, Nishio N, Ikehara S: Fate of allogeneic or syngeneic cells in intravenous or portal vein injection: Possible explanation for the mechanism of tolerance induction by portal vein injection. Eur J Immunol 1994;24:1558–1565.
17.
Sugiura K, Kato K, Hashimoto F, Jin T, Amoh Y, Yamamoto Y, Morita H, Okumura K, Ikehara S: Induction of donor-specific T cell anergy by portal venous injection of allogeneic cells. Immunobiology 1997;197:460–477.
18.
Morita H, Sugiura K, Inaba M, Jin T, Ishikawa J, Lian Z, Adachi Y, Sogo S, Yamanishi K, Taki H, Adachi M, Noumi T, Kaiyama Y, Good RA, Ikehara S: A strategy for organ allografts without using immunosuppressants or irradiation. Proc Natl Acad Sci USA 1998;95:6947–6952.
19.
Kushida T, Inaba M, Takeuchi K, Sugiura K, Ogawa R, Ikehara S: Treatment of intractable autoimmune diseases in mRL/lpr mice using a new strategy for allogeneic bone marrow transplantation. Blood 2000;95:1862–1868.
20.
Kushida T, Inaba M, Hisha H, Ichioka N, Ogawa R, Ikehara S: Crucial role of donor-derived stromal cells in successful treatment for intractable autoimmune diseases in MRL/lpr mice by BMT via portal vein. Stem Cells, in press.
21.
Fan T, Hisha H, Jin T, Yu C, Lian Z, Guo S, Cui Y, Feng B, Yang G, Li Q, Ikehara S: Successful allogeneic bone marrow transplantation (BMT) by injection of bone marrow cells via portal vein: Stromal cells as BMT-facilitating cells. Stem Cells 2001;19:144–150.
22.
Kushida T, Inaba M, Hisha H, Ichioka N, Ogawa R, Ikehara S. Intra-bone marrow injection of allogeneic bone marrow cells: A powerful new stragegy for treatment of intractable autoimmune diseases in MRL/lpr mice. Blood, in press.
23.
Li Y, Hisha H, Inaba M, Lian Z, Yu C, Kawamura M, Yamamoto Y, Nishio N, TokiJ, Fan H, Ikehara S: Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection. Exp Hematol 2000;28:950–960.
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.