Eluting matrix and uses thereof
CXCL12 polypeptide eluting matrices encapsulating at least one cell are described for use in the treatment of autoimmune disorders.
1. An eluting matrix suitable for implantation into a mammal, said matrix comprising at least one insulin producing cell,
wherein said cell is encapsulated in a CXCL12-eluting porous alginate matrix which is permeable to the insulin, and further
wherein the elution rate of CXCL12 from the matrix is from 1 ng/mL/hr to 3 ng/mL/hr so as to repel effector T-cells surrounding said matrix for a period of at least one month after implantation.
2. The eluting matrix of claim 1 , wherein the elution rate of CXCL12 is 1.75 ng/mL/hr.
3. The eluting matrix of claim 1 , wherein the CXCL12 is present in the matrix at a concentration of at least about 100 ng/mL.
4. The eluting matrix of claim 1 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL.
5. The eluting matrix of claim 4 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL for about 3 months to about 2 years after implantation.
6. The eluting matrix of claim 1 , wherein the matrix has a thickness of from about 200 microns to about 500 microns.
7. The eluting matrix of claim 1 , further comprising a secondary layer of cells that express a CXCL12 polypeptide.
8. The eluting matrix of claim 1 , further comprising an outer layer of a CXCL12 polypeptide.
9. The eluting matrix of claim 1 , wherein said at least one cell is selected from the group consisting of a myocyte, a fibroblast, a chondrocyte, an adipocyte, a fibromyoblast, an ectodermal cell, a kidney cell, a liver cell, a pancreatic cell, an intestinal cell, an osteoblast, and a hematopoietic cell.
10. The eluting matrix of claim 1 , wherein said at least one cell is selected from the group consisting of a neuronal cell, a smooth muscle cell, a skeletal muscle cell, a cardiac cell, an epithelial cell, and a hepatocyte.
11. The eluting matrices of claim 1 , wherein said at least one cell is a stem cell.
12. An eluting matrix suitable for implantation into a mammal, said matrix comprising at least one xenogenic islet cell capable of expressing insulin, wherein said cell is encapsulated in a CXCL12 eluting porous alginate matrix having a thickness of from 200 microns to 500 microns, and
further wherein the elution rate of CXCL12 is from 1 ng/mL/hr to 3 ng/mL/hr thereby providing a fugetactic environment surrounding said composition which is maintained for a period of at least one month after implantation and wherein said matrix is permeable to the insulin expressed by said cell.
13. The eluting matrix of claim 12 , wherein the elution rate of CXCL12 is 1.75 ng/mL/hr.
14. The eluting matrix of claim 12 , wherein the CXCL12 is present in the matrix at a concentration of at least about 100 ng/mL.
15. The eluting matrix of claim 12 , wherein the CXCL12 as present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL.
16. The eluting matrix of claim 12 , wherein the CXCL12 is present in the matrix at a concentration of between about 100 ng/mL to about 1 μg/mL for about 3 months to about 2 years after implantation.
17. The eluting matrix of claim 12 , wherein said alginate matrix is covalently crosslinked.
18. The eluting matrix of claim 12 , wherein said matrix comprise about 1.5 to about 2% w/v of a high mannuronic acid, calcium cross-linked alginate.
19. The elating matrix of claim 12 , wherein said alginate matrix is comprised of alginate polymer subunits having an average molecular weight of less than 75 kDa.
20. The eluting matrix of claim 12 , wherein said alginate matrix is comprised of alginate polymer subunits having an average molecular weight of about 75 kDa to about 200 kDa.
21. The eluting matrix of claim 12 , wherein said alginate matrix is comprised of mannuronic acid and guluronic acid.
22. The eluting matrix of claim 21 , wherein said alginate matrix comprises a mannuronic acid to guluronic acid ratio of about 1:100 to about 100.1.
23. The eluting matrix of claim 21 , wherein said alginate matrix comprises a guluronic acid to mannuronic acid ratio of no more than 3:2.