Ex vivo spermine dialdehyde treatment prevents lethal GVHD in a murine bone marrow transplantation model.
Spermine dialdehyde (SDA), an oxidized product of spermine which irreversibly suppresses T cell and NK cell activities, was evaluated as an ex vivo purging agent in the prevention of graft-versus-host disease (GVHD) in mice transplanted with SDA-treated allogeneic bone marrow. In this model, lethally irradiated C3H (H-2k) mice received BALB/c (H-2d) bone marrow and spleen cell mixtures which had been treated ex vivo for 10 min with SDA. Mice receiving SDA-treated cells survived past 100 days whereas mice in the control group died between days 25-35 suffering from severe GVHD. Surviving mice from the SDA-treated groups exhibited full chimerism at day 120. In vitro assays indicated that SDA inhibited T cell and NK cell activities at concentrations that spared myeloid cell growth. When a minimum number of bone marrow cells were used for reconstitution, SDA-treated marrow reconstituted lethally irradiated mice as effectively as control marrow suggesting that SDA had little impact on early myeloid cells which are required for engraftment. SDA may have clinical application as a purging agent in allogeneic bone marrow transplantation.
Wang
E
E
Biological Research Department, R. W. Johnson Pharmaceutical Research Institute, Ortho Pharmaceutical Ltd, Ontario, Canada.
Conant
J M
JM
Li
D
D
Visconti
V
V
Chourmouzis
E
E
Lau
C
C
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002678:Chimera / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D013096:Spermine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects; D014184:Transplantation, Homologous
C050864:N,N'-bis(3-propionaldehyde)-1,4-diaminobutane; D013096:Spermine