Expansion of haemopoietic precursors
View Patent ↗The present invention relates to a method of transplanting haematopoietic precursor cells into a subject in need thereof which involves culturing the haematopoietic precursor cells in the presence of a population of cells enriched for STRO-1 bright cells. The method of the present invention is useful in the treatment of haematological disorders.
1. A method of transplanting haematopoietic precursor cells into a subject in need thereof, the method comprising:
culturing haematopoietic precursor cells in the presence of a population of cells enriched for STRO-1 bright cells or supernatant or progeny derived therefrom, wherein such STRO-1 bright cells are mesenchymal precursor cells (MPC) which comprise mesenchymal precursor cells capable of giving rise to colony forming unit-fibroblasts (CFU-F), so as to expand the haematopoietic precursor cells; and
administering the expanded haematopoietic precursor cells to a subject,
wherein haematopoietic reconstitution occurs in the subject within 10 to 30 days of administration of the expanded haematopoietic precursor cells.
2. The method of claim 1 , wherein the population of cells enriched for STRO-1 bright cells are allogeneic cells.
3. The method of claim 1 wherein the expanded haematopoietic precursor cells comprise CFU-GM cells.
4. The method of claim 1 wherein haematopoietic reconstitution occurs in the absence of an adverse immune response.
5. The method of claim 1 wherein haematopoietic reconstitution is determined by neutrophil engraftment, platelet engraftment, lymphoid engraftment, erythroid engraftment and/or megakaryocyte engraftment.
6. The method of claim 1 which further comprises administering to the subject a factor which enhances differentiation of the haematopoietic precursor cells to a specific haematopoietic lineage cell.
7. The method of claim 6 wherein the haematopoietic lineage cell is a B-cell, T-cell, dendritic cell, monocyte, neutrophil, macrophage, natural killer cell, granulocyte, erythrocyte, eosinophil, megakaryocyte, platelet, bone marrow, splenic, dermal, or stromal cell.
8. The method of claim 6 wherein the factor which enhances differentiation is stem cell factor (SCF), GM-SCF, M-CSF, G-CSF, MGDF, EPO, FLT3-ligand, IL-1, IL-2, IL-3, IL-4, IL-6, IL-7, IL-11, TNFα, or thrombopoietin.
9. The method claim 1 wherein administering the expanded haematopoietic precursor cells reduces the risk of host versus graft disease when compared to administration of haematopoietic precursor cells that have not been subject to ex vivo expansion.
10. The method of claim 1 wherein the subject has a haematologic disorder.
11. The method of claim 10 wherein the haematologic disorder is a disorder of platelet number and/or function.
12. The method of claim 11 wherein the haematologic disorder is thrombocytopenia, idiopathic thrombocytopenic purpure (ITP), or a disorder related to viral infection, drug abuse or malignancy.
13. The method of claim 10 wherein the haematologic disorder is a disorder of erythrocyte number and/or function.
14. The method of claim 13 wherein the haematologic disorder is an anaemia.
15. The method of claim 14 wherein the anaemia is aplastic anaemia, autoimmune haemolytic anaemia, blood loss anaemia, Cooley's anaemia, Diamond-Blackfan anaemia, Fanconi anaemia, folate (folic acid) deficiency anaemia, haemolytic anaemia, iron-deficiency anaemia, pernicious anaemia, sickle cell anaemia, thalassaemia or Polycythemia Vera.
16. The method of claim 10 wherein the haematologic disorder is a disorder of lymphocyte number and/or function.
17. The method of claim 16 wherein the disorder is due to a T-cell or B-cell deficiency.
18. The method of claim 16 wherein the disorder is AIDS, a leukemia, a lymphoma, Hodgkins lumphoma, a chronic infection such as military tuberculosis, a viral infection, rheumatoid arthritis, systemic lupus erythaematosus, or a hereditary disorder such as agammaglobulinemia, DiGeorge anomaly, Wiskott-Aldrich syndrome, or ataxia-telangiectasia.
19. The method of claim 10 wherein the haematologic disorder is a disorder of multilineage bone marrow failure.
20. The method of claim 19 wherein the haematologic disorder is a result of radiotherapy or chemotherapy.
21. The method of claim 19 wherein the haematologic disorder is a result of malignant replacement.
22. The method of claim 21 wherein the haematologic disorder is myelofibrosis, acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), chromic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), Non-Hodgkin's lymphoma (NHL), Hodgkin's Disease (HD), multiple myeloma, or a secondary malignancy disseminated to bone.