This project represents continuation of an effort using experimental analysis to perfect allogeneic bone marrow transplantation for treatment and prevention of diseases Clinically allogeneic bone marrow transplantation based on experimental analyses in animals has become an accepted treatment for some 50 otherwise lethal diseases. Use of marrow transplantation has shown logarithmic growth since we performed the first successful allogeneic marrow transplants using matched sibling donors more than 18 years ago. Following leads of Israeli colleagues we developed in collaboration with Resiner marrow purging approaches that used lectin agglutination and E-rosetting plus differential centrifugation to make possible HLA haploidentical transplants when HLA matched sibling donors were not available. Current investigations focus on exploring means for marrow transplantation additional to autologous, syngeneic, MHC matched allogeneic or T- cell purged MHC haploidentical donors. We developed a new model which seems to permit allogeneic marrow transplantation in mice of MHC mismatched marrow. The method depends on first tolerizing prospective donors plus purging the marrow of T cells and T precursors with anti Thy- 1 + C. We will investigate whether this model is applicable to treatment and prevention of autoimmune disease in BXSB mice and of disease in each of several other autoimmune-prone strains. We will also test this approach to prepare long term chimerism in autoimmune-resistant mice and compare crucial immunological functions in the chimeras where recipients are autoimmune-prone or autoimmunity resistant. We will determine whether bone marrow transplants from congenic resistant, allogeneic MHC matched resistant, or MHC mismatched resistant marrow donors can permit prevention or facilitate treatment of breast canter in mice. Using marrow transplants from congenic senility-resistant, HLA matched or HLA mismatched senility - resistant mice we will try to influence development of manisfestation of senility in a new senility-accelerated mutant SAM(P). We will explore bone marrow transplantation to make possible organ transplantation without continuous treatment with immunosuppressive and determine whether bone marrow transplantation can introduce mechanisms of resistance to development of atherosclerosis and coronary vascular disease in auto-immunity- prone mice. We will continue ongoing research to understand the molecular basis for B cell abnormalities in auto-immune prone mice.
| Yamamoto, Yoshihisa; Wang, Bingyan; Fukuhara, Shirou et al. (2002) Mixed peripheral blood stem cell transplantation for autoimmune disease in BXSB/MpJ mice. Blood 100:1886-93 |
| Noguchi, M; Ogasawara, M; Iwabuchi, K et al. (1985) Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice. J Immunol 135:2557-61 |
