Methods and compositions for the repair and/or regeneration of damaged myocardium
Methods, compositions, and kits for repairing damaged myocardium and/or myocardial cells including the administration of stem cells, such as adult stem cells, optionally with cytokines are disclosed and claimed.
1. A method for repairing structure and function of damaged myocardium in a patient in need thereof comprising:
administering an effective dose of adult hematopoietic stem cells to the patient's heart, wherein said adult hematopoietic stem cells are lineage negative and c-kit positive and are isolated from a bone marrow specimen, and wherein the structure and function of the damaged myocardium is at least partially restored following stem cell administration.
2. The method of claim 1 , wherein the adult hematopoietic stem cells migrate into the damaged myocardium.
3. The method of claim 1 , wherein the bone marrow specimen is obtained from the patient to whom the isolated adult hematopoietic stem cells are administered.
4. The method of claim 1 , wherein the isolated adult hematopoietic stem cells are administered by injection.
5. The method of claim 4 , wherein the injection is intramyocardial.
6. The method of claim 4 , wherein the injection is trans-epicardial or transendocardial.
7. The method of claim 1 , wherein the isolated adult hematopoietic stem cells are administered by a catheter.
8. The method of claim 1 , wherein the effective dose of isolated adult hematopoietic stem cells is from about 2×10 4 to 1×10 5 .
9. The method of claim 1 , further comprising the administration of an effective dose of one or more cytokines.
10. The method of claim 9 , wherein the one or more cytokines is selected from the group consisting of:
(a) stem cell factor;
(b) granulocyte-colony stimulating factor;
(c) stromal cell-derived factor-1;
(d) interleukin-3;
(e) granulocyte-macrophage colony stimulating factor;
(f) macrophage colony stimulating factor;
(g) vascular endothelial cell growth factor;
and combinations thereof.
11. The method of claim 10 , wherein the administered cytokines are stem cell factor and granulocyte colony stimulating factor.
12. The method of claim 9 , wherein the effective dose of one or more cytokines is from 50 μg/kg to 500 μg/kg.
13. The method of claim 9 , wherein the effective dose of one or more cytokines is administered in multiple administrations.
14. The method of claim 13 , wherein the multiple administrations are given over the course of several days following the administration of the isolated adult hematopoietic stem cells.
15. The method of claim 9 , wherein the effective dose of one or more cytokines is administered systemically to the patient.
16. The method of claim 15 , wherein the systemic administration is subcutaneous or intravenous injection.
17. The method of claim 9 , wherein the administration of one or more cytokines stimulates the patient's resident hematopoietic stem cells causing them to mobilize into the bloodstream.
18. The method of claim 1 , wherein the isolated adult hematopoietic stem cells are administered to a border region of the damaged myocardium within the patient's heart.
19. The method of claim 1 , wherein the isolated adult hematopoietic stem cells are administered intraarterially.
20. The method of claim 1 , wherein the damaged myocardium is an infarction.
21. The method of claim 1 , wherein the isolated adult hematopoietic stem cells do not express CD4, CD8, B-220, Mac-1, GR-1, or TER-119.