PMID- 11342461 OWN - NLM STAT- MEDLINE DCOM- 20010614 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 97 IP - 10 DP - 2001 May 15 TI - Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice. PG - 3292-9 AB - 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. FAU - Kushida, T AU - Kushida T AD - First Department of Pathology, Transplantation Center, Kansai Medical University, Moriguchi City, Osaka, Japan. FAU - Inaba, M AU - Inaba M FAU - Hisha, H AU - Hisha H FAU - Ichioka, N AU - Ichioka N FAU - Esumi, T AU - Esumi T FAU - Ogawa, R AU - Ogawa R FAU - Iida, H AU - Iida H FAU - Ikehara, S AU - Ikehara S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Autoantibodies) SB - IM MH - Animals MH - Autoantibodies/blood MH - Autoimmune Diseases/mortality/*surgery MH - *Bone Marrow MH - Bone Marrow Cells MH - Bone Marrow Transplantation/*methods MH - Cell Count MH - Female MH - Hematopoietic Stem Cells MH - Injections MH - Liver/cytology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Spleen/cytology MH - Stromal Cells MH - Survival Rate MH - T-Lymphocytes/pathology MH - Tissue Donors EDAT- 2001/05/09 10:00 MHDA- 2001/06/15 10:01 CRDT- 2001/05/09 10:00 PHST- 2001/05/09 10:00 [pubmed] PHST- 2001/06/15 10:01 [medline] PHST- 2001/05/09 10:00 [entrez] AID - S0006-4971(20)55655-3 [pii] AID - 10.1182/blood.v97.10.3292 [doi] PST - ppublish SO - Blood. 2001 May 15;97(10):3292-9. doi: 10.1182/blood.v97.10.3292.