We propose to continue long-term efforts to perfect bone marrow transplantation (BMT) as a means to prevent or treat many different diseases. This series of systematic experimental investigations will explore further the usefulness of bone marrow or fetal liver cell transplantation and ultimately stem cell transplantation as an experimental approach to analysis, prevention or treatment of a number of diseases and disorders not yet effectively treated. First we will explore BMT as an approach to prevention or to causation of senility in mice. We will try to prevent senility associated disease or disorders, including amyloid deposition and arthritis or arthroses, in senility accelerated mice [SAM(P)] mice. Alternatively, congenic or allogeneic BMT or congenic or allogeneic neonatal liver transplantation will be tested as a means of introducing from SAM(P) into the congenic resistant SAM(R) mice the senility accelerating propensity. Similarly, BMT will be tested as a means of causing, preventing or treating senility-associated changes and amyloidosis when BMT donors share the major histocompatibility complex (MHC) but are allogeneic to the SAM(P) mice, e.g. CBA/H or C3H/He. Alternatively, we will attempt to use donors that differ from SAM(P) at MHC, e.g. C57B1/6. BMT will also be tested as a means of preventing or treating two new models of non-inflammatory coronary vascular diseases or atherosclerosis in inbred mice. We will compare the immunological consequences of long-term BMT induced chimeric state where BMT have either been performed from autoimmune-resistant donors to mice of autoimmune-prone strains or to mice of autoimmune-resistant strains. We will also ascertain whether it is possible to treat effectively by BMT advanced, putatively irreversible kidney disease associated with autoimmunity states. Experiments will attempt to employ BMT from MHC-matched, MHC-mismatched or haploidentical donors to treat effectively advanced kidney disease by complete correction by BMT of the autoimmunity and immunologic dysregulation that led to the kidney disease in the first place. Finally, we will initiate experiments to evaluate the potential of stem cell preparations to reconstruct the entire hematopoietic and lymphoid systems and immunologic functions as an approach to correcting the genetically determined propensity to develop autoimmunities nad other diseases associated with aging and to analyze and influence the abnormal accumulations of Ly1+ B lymphocytes that occur in these autoimmune states.
| Kirzner, R P; Engelman, R W; Mizutani, H et al. (2000) Prevention of coronary vascular disease by transplantation of T-cell-depleted bone marrow and hematopoietic stem cell preparation in autoimmune-prone w/BF(1) mice. Biol Blood Marrow Transplant 6:513-22 |
