Engineered extracellular matrices control stem cell behavior
A composition for culturing stem cells is provided. The composition comprises an engineered purified collagen based matrix that has been formed under controlled conditions to have the desired microstructure and mechanical properties. The engineered purified collagen based matrix compositions of the present invention can be used alone or in combination with cells as a tissue graft construct to enhance the repair of damaged or diseased tissues.
1. A tissue graft composition, said composition comprising
a synthetic collagen-based matrix comprising collagen fibrils, wherein the matrix has an elastic or linear modulus of about 0.5 kPa to about 40 kPa; and
a population of mesenchymal stem cells,
wherein the matrix is prepared by a process comprising the step of controlling the elastic or linear modulus to make the stem cells adipogenic or osteogenic.
2. The composition of claim 1 wherein the step of controlling the elastic or linear modulus makes the stem cells adipogenic.
3. The composition of claim 1 wherein the step of controlling the elastic or linear modulus makes the stem cells osteogenic.
4. The composition of claim 2 wherein the matrix is a purified collagen matrix.
5. The composition of claim 3 wherein the matrix is a purified collagen matrix.
6. The composition of claim 2 wherein the collagen is enzymatically digested.
7. The composition of claim 6 wherein the collagen is protease digested.
8. The composition of claim 3 wherein the collagen is enzymatically digested.
9. The composition of claim 8 wherein the collagen is protease digested.
10. The composition of claim 2 wherein the collagen is not enzymatically digested.
11. The composition of claim 3 wherein the collagen is not enzymatically digested.
12. The composition of claim 2 wherein the collagen is solubilized collagen.
13. The composition of claim 3 wherein the collagen is solubilized collagen.
14. The composition of claim 2 wherein the fibril area fraction of the matrix is about 7% to about 26%.
15. The composition of claim 3 wherein the fibril area fraction of the matrix is about 7% to about 26%.
16. The composition of claim 2 wherein the matrix is sterile.
17. The composition of claim 3 wherein the matrix is sterile.
18. The composition of claim 2 wherein the composition further comprises a glycoprotein, a proteoglycan, or a glycosaminoglycan.
19. The composition of claim 3 wherein the composition further comprises a glycoprotein, a proteoglycan, or a glycosaminoglycan.
20. The composition of claim 2 wherein the composition further comprises a cell culture medium and wherein the cells are at a density of less than 5×10 4 cells per milliliter of the medium.
21. The composition of claim 3 wherein the composition further comprises a cell culture medium and wherein the cells are at a density of less than 5×10 4 cells per milliliter of the medium.
22. The composition of claim 2 wherein the composition further comprises a sterile package.
23. The composition of claim 3 wherein the composition further comprises a sterile package.
24. The composition of claim 1 wherein the matrix has an elastic or linear modulus of about 0.5 kPa to about 24 kPa.
25. The composition of claim 1 wherein the matrix has an elastic or linear modulus of about 25 kPa to about 40 kPa.