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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3292-3299
TRANSPLANTATION
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, and
Susumu Ikehara
From the First Department of Pathology; and Department
of Orthopedic Surgery, Transplantation Center, Kansai Medical
University, Moriguchi City, Osaka, Japan.
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 × 2, followed by
intra-bone marrow (IBM) injection of whole bone marrow cells (BMCs)
from allogeneic normal C57BL/6 (B6) mice (5.5 Gy × 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 × 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.
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