Engineered physical alignment of stem cell-derived cardiomyocytes
View Patent ↗Provided are devices and methods of preparing a population of cardiomyocytes by aligning undifferentiated pluripotent cells on a nanosacale textured surface.
1. An isolated population of cardiomyocytes prepared by a method comprising aligning stem cells on a three-dimensional concave, micro-textured surface and culturing the aligned stem cells under conditions suitable for the stem cells to differentiate into the isolated population of cardiomyocytes, wherein the three-dimensional concave, micro-textured surface 1) conforms to an interior surface of a balloon and 2) includes at least about 10% of a sphere, and wherein the population of cardiomyocytes produces functional anisotropy.
2. The isolated population of claim 1 , wherein the population comprises ventricular cardiomyocytes.
3. The isolated population of claim 1 , wherein the population comprises ventricular cardiomyocytes and fibroblasts.
4. The isolated population of claim 3 , wherein the population comprises ventricular cardiomyocytes and fibroblasts at a ratio selected from the group consisting of 1:1; 2:1; and 1:2.
5. The isolated population of claim 1 , wherein the surface is prepared by a method comprising soft-lithography of a plasma-treated micro-textured master with grooved surface features to impose contact guidance cues during chamber creation.
6. The isolated population of claim 5 , wherein the stem cells are prepared by differentiating a composition comprising one or more of an embryonic stem cell, an induced pluripotent stem cell (iPSCs) and an adult stem cell.
7. The isolated population of claim 1 , wherein the surface is prepared by a method comprising soft-lithography of a plasma-treated textured balloon with grooved surface features to impose contact guidance cues during chamber creation.
8. The isolated population of claim 7 , wherein the stem cells are prepared by differentiating a composition comprising one or more of an embryonic stem cell, an induced pluripotent stem cell (iPSCs) and an adult stem cell.
9. The isolated population claim 1 , wherein the stem cells are mammalian or human stem cells.
10. The isolated population of claim 9 , wherein the stem cells are prepared by differentiating a composition comprising one or more of an embryonic stem cell, an induced pluripotent stem cell (iPSCs) and an adult stem cell.
11. The isolated population of claim 1 , wherein the stem cells are prepared by differentiating a composition comprising one or more of an embryonic stem cell, an induced pluripotent stem cell (iPSCs) and an adult stem cell.
12. The isolated population of claim 1 , wherein the stem cells are prepared by differentiating a composition comprising one or more of an embryonic stem cell, an induced pluripotent stem cell (iPSCs) and an adult stem cell.
13. A method of preparing an isolated population of cardiomyocytes, comprising aligning stem cells on a three-dimensional concave, micro-textured surface and culturing the aligned stem cells under conditions suitable for the stem cells to differentiate into the isolated population of cardiomyocytes, wherein the three-dimensional concave, micro-textured surface 1) conforms to an interior surface of a balloon and 2) includes at least about 10% of a sphere, and wherein the population of cardiomyocytes produces functional anisotropy.
14. The method of claim 13 , further comprising, prior to culturing the stem cells on the textured surface, preparing the textured surface with a method comprising treating a thermoplastic material with plasma, shrinking the treated thermoplastic material to obtain a textured surface, replicating the textured surface using soft lithography to a scaffold to generate a textured surface on the scaffold, and subjecting the scaffold to a pressure to render the surface of the scaffold concave.
15. The method of claim 14 , wherein the thermoplastic material is treated with the plasma for about 5 minutes.
16. The method of claim 14 , wherein only one side of the thermoplastic material is treated with the plasma.
17. The method of claim 14 , wherein the plasma is oxygen plasma.
18. The method of claim 14 , wherein the aligned cardiomyocytes are ventricular myocytes.
19. The method of claim 18 , wherein the aligned ventricular cardiomyocytes have at least one of a transverse conduction velocity of from about 2 to about 4 cm/s at 1 HZ or a longitudinal conduction velocity of from about 3 to 8 cm/s at 1 HZ.
20. The method of claim 18 , wherein the aligned ventricular cardiomyocytes have an average anisotropy ratio (AR) of from about 0.5 to 1.5.
21. The method of claim 13 , wherein the aligned cardiomyocytes are ventricular myocytes.
22. The method of claim 21 , wherein the aligned ventricular cardiomyocytes have at least one of a transverse conduction velocity of from about 2 to about 4 cm/s at 1 HZ or a longitudinal conduction velocity of from about 3 to 8 cm/s at 1 HZ.