Allogeneic intra-bone marrow transplantation prevents rheumatoid arthritis in SKG/Jcl mice.
The treatment of autoimmune diseases by allogeneic bone marrow transplantation remains a promising therapeutic avenue. However, more intensive studies on murine models are essential before application to a large number of human patients. In particular, the use of bone marrow transplantation to treat rheumatoid arthritis has been problematic. We have taken advantage of the SKG/Jcl mouse that develops a chronic T cell-mediated autoimmune disease that mimics rheumatoid arthritis which attempted to prevent the development of immunopathology in these mice by allogeneic bone marrow transplantation (BMT). In particular, we utilized our unique technology in which bone marrow cells (BMCs) of control C57BL/6J mice are directly injected into the bone marrow cavity in the tibia of SKG mice (intra-bone marrow [IBM]-BMT). As controls, SKG/Jcl mice were transplanted with whole BMCs from syngeneic SKG mice. Importantly, 12 months after IBM-BMT [B6-->SKG] demonstrated no evidence of arthritis, whereas the control [SKG-->SKG] mice demonstrated, the expected immunopathology of a rheumatoid arthritis-like condition. Further, hematolymphoid cells in [B6-->SKG] mice were reconstituted by donor-derived cells and the percentages of Treg (Foxp3+/CD4+) cells, the percentages of receptor activator of nuclear factor-kappaB ligand (RANKL)+ cells on the CD4+ T cells and the serum levels of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 were normalized in the [B6-->SKG] mice. These data suggest that IBM-BMT is a viable method of immunological manipulation that suppresses the severe joint destruction and bone absorption in SKG/Jcl mice and lends further credence to the use of this methodology in humans with intractable rheumatoid arthritis.
Department of Orthopedic Surgery, Kansai Medical University, Moriguchi City, Osaka 570-8506, Japan.
Taketoshi
T
Kushida
Yusuke
Y
Ueda
Masayuki
M
Umeda
Kenichi
K
Oe
Naofumi
N
Okamoto
Hirokazu
H
Iida
Nader G
NG
Abraham
M Eric
ME
Gershwin
Susumu
S
Ikehara
D000596:Amino Acids / Q000652:urine; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000517:prevention & control / Q000601:surgery*; D016026:Bone Marrow Transplantation; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D053245:RANK Ligand / Q000378:metabolism; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000596:Amino Acids; D007375:Interleukin-1; D015850:Interleukin-6; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C036020:deoxypyridinoline