Bone marrow cultures for developing suppressor and stimulator cells for research and therapeutic applications
AssigneesUniversity of Cincinnati, Shriners Hospitals for Children
InventorsCora K. Ogle, John F. Valente, J. Wesley Alexander
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Abstract
A method of treatment using immune system suppressor cells and immune system stimulator cells comprises providing stem cells; combining the stem cells with lymphoid-derived cells to produce a co-culture; adding lipopolysaccharide and a factor selected from the group consisting of granulocyte macrophage-colony stimulating factor, macrophage colony stimulating factor, granulocyte-colony stimulating factor and mixtures thereof to the co-culture; obtaining immune system suppressor cells and immune system stimulator cells from the co-culture; and introducing and the cells into a host.
Claims20
A method of treatment comprising the steps of:
- (a) obtaining stem cells from bone marrow;
- (b) combining the stem cells with splenocytes to form a co-culture;
- (c) adding a first factor selected from the group consisting of lipopolysaccharide, interleukin-6, interleukin-4, tumor necrosis factor alpha, transforming growth factor beta, anti-CD3 and mixtures thereof to the co-culture;
- (d) adding a second factor selected from the group consisting of granulocyte macrophage colony-stimulating factor, macrophage-colony stimulating factor, granulocyte-colony stimulating factor, FLT3 ligand and mixtures thereof to the co-culture;
- (e) maintaining the co-culture for at least 4 days;
- (f) obtaining differentiated immune system suppressor cells and immune system stimulator cells from the co-culture;
- and
- (g) introducing the immune system suppressor cells and immune system stimulatory cells into a host;
- wherein the immune system suppressor cells are capable of prolonging allograft survival when infused as a donor specific transfusion to a transplant patient.
A method of reducing the amounts of general immunosuppressive drugs given to a transplant patient, comprising the steps of:
- a) removing bone marrow;
- b) obtaining a first population of cells from the bone marrow, wherein the first population of cells are stem cells;
- c) combining the stem cells with a second cell population derived from lymphoid tissue to produce a co-culture;
- d) adding granulocyte macrophage-colony stimulating factor and lipopolysaccharide to the co-culture;
- e) allowing the stem cells to differentiate;
- f) obtaining immune system suppressor cells from the co-culture;
- g) administering to a transplant patient the immune system suppressor cells and a third population of cells, wherein the third population of cells are dendritic cells selected from the group consisting of dendritic cells of splenic, bone marrow, blood, liver and fetal liver origin, and mixtures thereof;
- wherein the immune system suppressor cells are capable of prolonging graft survival in the transplant patient.
A method of treatment comprising the steps of:
- a) obtaining stem cells from bone marrow;
- b) combining the stem cells with splenocytes in medium to form a co-culture;
- c) adding to the medium granulocyte macrophage-colony stimulating factor at a level of 100 units/ml medium, and lipopolysaccharide at a level of 1 .mu.g/ml medium;
- d) maintaining the co-culture for from 4 to 14 days;
- e) obtaining differentiated immune system suppressor cells from the co-culture;
- f) introducing the immune system suppressor cells into a host;
- and
- g) substantially contemporaneously introducing an enriched population splenic of dendritic cells into the host;
- wherein the immune system suppressor cells are capable of prolonging allograft survival when infused as a donor specific transfusion to a transplant patient.
Dependencies are inferred from the claim text.