Formulation to improve survival of transplanted cells
The survival of cells during transplantation is enhanced. Cells to be transplanted are administered in a formulation that provides two ore more survival enhancing factors. Optionally, prior to administration, the cells are cultured in the presence of factors that enhance survival, and may be heat shocked prior to transplantation.
1. A method for the transplantation of mammalian cells, the method comprising:
administering to an individual a cellular composition comprising mammalian cells selected from stem cells, progenitor cells and cardiomyocytes in a fluid suspension comprising solubilized basement membrane proteins, an immunosuppressive agent, a pan-caspase inhibitor, an anti-apoptotic agent, IGF-1, and a K ATP channel opening agent,
wherein said mammalian cells are heat-shocked prior to said transplantation.
2. The method according to claim 1 , wherein said mammalian cells are cultured in vitro.
3. The method according to claim 1 , wherein said mammalian cells are derived from embryonic stem cells in vitro.
4. The method according to claim 3 , wherein said mammalian cells are cardiomyocytes.
5. The method according to claim 1 , wherein said mammalian stem or progenitor cells are cultured in the presence of an anti-inflammatory agent and an IGF1R ligand prior to said transplantation.
6. The method according to claim 1 , wherein the solubilized basement membrane protein is present at a concentration of from 2.5 mg/ml to 8 mg/ml.
7. The method according to claim 1 , wherein the immunosuppressive agent is cyclosporine, and is present at a concentration of at least 10 nM and not more than 1 μM.
8. The method according to claim 1 , wherein the pan-caspase inhibitor is present at a concentration of at least 2.5 mg/ml and not more than 8 mg/ml.
9. The method according to claim 1 , wherein the IGF-1 is present at a concentration of at least 1 μg/ml and not more than 1 μg/ml.
10. The method according to claim 1 , wherein the anti-apoptotic agent is the BH4 peptide domain of Bcl-X L at a concentration of at least 0.1 nM and not more than 10 μM.
11. The method according to claim 1 , wherein the K ATP channel opening agent is pinacidil at a concentration of at least 1 μM and not more than 1 mM.
12. A method for the transplantation of mammalian cardiomyocytes, the method comprising:
administering to an individual a cellular composition comprising cardiomyocytes cultured in vitro in the presence of an anti-inflammatory agent and an IGF1R ligand; in a fluid suspension comprising solubilized basement membrane proteins, an immunosuppressive agent, a pan-caspase inhibitor, an anti-apoptotic agent, IGF-1, and a K ATP channel opening agent,
wherein said mammalian cells are heat-shocked prior to said transplantation.
13. The method according to claim 12 , wherein the solubilized basement membrane protein is present at a concentration of from 2.5 mg/ml to 8 mg/ml.
14. The method according to claim 12 , wherein the immunosuppressive agent is cyclosporine, and is present at a concentration of at least 10 nM and not more than 1 μM.
15. The method according to claim 12 , wherein the pan-caspase inhibitor is present at a concentration of at least 2.5 mg/ml and not more than 8 mg/ml.
16. The method according to claim 12 , wherein the IGF-1 is present at a concentration of at least 1 ng/ml and not more than 1 μg/ml.
17. The method according to claim 12 , wherein the anti-apoptotic agent is the BH4 peptide domain of Bcl-X L at a concentration of at least 0.1 nM and not more than 10 μM.
18. The method according to claim 12 , wherein the K ATP channel opening agent is pinacidil at a concentration of at least 1 μM and not more than 1 mM.