Parathyroid hormone receptor activation and hematopoietic progenitor cell expansion
The invention relates to methods for manipulating hematopoietic progenitor cells and related products. In one aspect the invention relates to the use of agents that activate a PTH/PTHrP receptor to enhance the growth and maintenance of hematopoietic progenitor cells in vivo and in vitro, to enhance mobilization of hematopoietic stem cells, to improve the efficiency of targeting cells to the bone marrow, and/or to modulate hematopoietic progenitor cell function.
1. A method for enhancing the growth or maintenance of hematopoietic progenitor cells in a subject, the method comprising:
administering to a subject in need of hematopoietic cell growth or maintenance an agent that activates the PTH/PTHrP receptor in cells of the subject expressing the PTH/PTHrP receptor, in an amount and for a duration effective to support the growth or maintenance of hematopoietic progenitor cells, wherein the subject is a bone marrow donor who has donated bone marrow, is a bone marrow donor who has yet to donate bone marrow, is a bone marrow transplant recipient, has hematopoietic progenitor cells under environmental stress, or has anemia.
2. The method of claim 1 , wherein the cell expressing a PTH/PTHrP receptor is chosen from an osteoblast, epithelial cell, endothelial cell, mesothelial cell, dendritic cell, spenocyte, macrophage, a lymphoreticular stromal cell, and a mixture of osteoblasts and lymphoreticular stromal cells.
3. The method of claim 1 , wherein the cell expressing a PTH/PTHrP receptor is a hematopoietic progenitor cell.
4. The method of claim 1 , wherein the agent that activates the PTH/PTHrP receptor is PTH, a PTH analogue, or a PTH/PTHrP receptor agonist.
5. A method for enhancing mobilization of hematopoletic progenitor cells, the method comprising:
administering to a subject in need of such treatment an agent that activates a PTH/PTHrP receptor in an amount and for a duration sufficient to enhance mobilization of hematopoletic progenitor cells in the subject, wherein the subject is a bone marrow donor who has donated bone marrow or is a bone marrow donor who has yet to donate bone marrow.
6. The method of claim 5 , wherein the cell expressing a PTH/PTHrP receptor is chosen from an osteoblast, epithelial cell, endothelial cell, mesothelial cell, dendritic cell, spenocyte, macrophage, a lymphoreticular stromal cell, and a mixture of osteoblasts and lymphoreticular stromal cells.
7. The method of claim 5 , wherein the cell expressing a PTH/PTHrP receptor is a hematopoietic progenitor cell.
8. The method of claim 5 , wherein the agent that activates the PTH/PTHrP receptor is PTH, a PTH analogue, or a PTH/PTHrP receptor agonist.
9. The method of claim 5 , wherein the agent is administered to the subject at least five times per week for four weeks.
10. The method of claim 1 , wherein the agent is administered to the subject at least five times per week for four weeks.