Regeneration of coronary artery by coronary endothelial specific progenitor cells
View Patent ↗Methods and products are provided for producing an artery-specific endothelial cell. Also provided are methods for treating a tumor in a subject.
1. A method for producing an artery-specific endothelial cell comprising contacting an Nfatc1+ endocardial cell with an amount of an agent that activates Vegfr-2 effective to produce an artery-specific endothelial cell from the Nfatc1+ endocardial cell.
2. The method of claim 1 , wherein the artery-specific endothelial cell is a coronary artery-specific endothelial cell.
3. The method of claim 1 , wherein the Nfatc1+ endocardial cell is contacted with the agent that activates Vegfr-2.
4. The method of claim 1 , wherein the Nfatc1+ endocardial cell is contacted with an agent that activates human Vegfr-2.
5. The method of claim 1 , wherein the agent that activates Vegfr-2 is Vegf-a.
6. The method of claim 5 , wherein the Vegf-a is human Vegf-a.
7. The method of claim 1 , wherein the endocardial cell is obtained from a ventricular endocardium.
8. A composition comprising a plurality of isolated artery-specific endothelial cells produced by the method of claim 1 .
9. The composition of claim 8 , wherein the composition is 90% or greater isolated artery-specific endothelial cells.
10. The composition of claim 9 , wherein the composition is 99% or greater isolated artery-specific endothelial cells.
11. A method of treating a heart condition in a mammalian subject comprising administering to the subject an amount of the artery-specific endothelial cells produced by claim 1 effective to treat the heart condition in a mammalian subject.
12. The method of claim 11 , wherein a symptom of the heart condition is a diseased coronary artery of the heart.
13. The method of claim 11 , wherein the heart condition is atherosclerosis or heart infarction.
14. A method of determining whether an agent specifically promotes the growth of coronary artery-specific endothelial cells comprising contacting an Nfatc1+ endocardial cell with an amount of an activator of Vegfr-2 or of Vegf-a under conditions permitting the cell to produce an artery-specific endothelial cell from the Nfatc1+ endocardial cell, and measuring the extent of growth of the artery-specific endothelial cell in the presence of, and in the absence of, the agent, wherein an increased growth of artery-specific endothelial cells in the presence of the agent as compared to in the absence of the agent indicates that the agent specifically promotes the growth of coronary artery-specific endothelial cells, and wherein a decreased, or no increase in, growth of artery-specific endothelial cells in the presence of the agent as compared to in the absence of the agent indicates that the agent does not specifically promote the growth of coronary artery-specific endothelial cells.
15. The method of claim 14 , wherein the agent is a small organic molecule, a peptide, an RNAi agent, a nucleic acid, an antibody or an antibody fragment.