TREATMENT OF RETINAL DEGENERATION USING PROGENITOR CELLS

• US 20170080033A1
• Filed: 12/01/2016
• Published: 03/23/2017
• Est. Priority Date: 12/16/2014
• Status: Abandoned Application

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Original Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Inventors: Harris, Ian R., Cao, Jing, Dejneka, Nadine
• Application Number:
  US15/366,947
• Publication Number:
  US 20170080033A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

Methods and compositions for treating and reducing retinal degeneration using progenitor cells and conditioned media from progenitor cells, such as postpartum-derived cells are disclosed. Trophic factors and other agents secreted by the progenitor cells that protect retinal cells and inhibit apoptosis of retinal cells such as photoreceptor cells are also disclosed.

Claims

1. A method of treating retinal degeneration comprising administering to the eye of a subject a population of postpartum-derived cells, wherein the cell population secretes bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.

3. The method of claim 1, wherein the population of postpartum-derived cells comprises human umbilical cord tissue-derived cells isolated from human umbilical cord tissue substantially free of blood.

4. The method of claim 3, wherein the cell population isolated from human umbilical cord tissue substantially free of blood is capable of expansion in culture, has the potential to differentiate into cells of at least a neural phenotype, maintains a normal karyotype upon passaging, and has the following characteristics:

a) potential for 40 population doublings in culture;

b) production of CD10, CD13, CD44, CD73, and CD90;

c) lack of production of CD31, CD34, CD45, CD117, and CD141, and

d) increased expression of genes encoding interleukin 8 and reticulon 1 relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

5. The method of claim 1, wherein the cell population secretes receptor tyrosine kinase (RTK) trophic factors.

6. The method of claim 5, wherein the trophic factors are BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

9. The method of claim 4, wherein the cell population secretes receptor tyrosine kinase (RTK) trophic factors selected from the group consisting of BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

21. The method of claim 1, wherein the retinal degeneration is age-related macular degeneration.

22. The method of claim 21, wherein the age-related macular degeneration is dry age-related macular degeneration.

24. The method of claim 4, wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

26. The method of claim 1, wherein administration to the eye is selected from administration to the interior of an eye or administration behind the eye.

2. A method of administering a population of postpartum-derived cells to the eye of a subject, wherein the cell population secretes bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.

7. The method of claim 2, wherein the cell population secretes receptor tyrosine kinase (RTK) trophic factors.

8. The method of claim 7, wherein the trophic factors are BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

10. A method of reducing retinal cell oxidative damage comprising administering to the eye of a subject a population of postpartum-derived cells or a conditioned medium generated by culturing the postpartum-derived cells, wherein the postpartum-derived cells are isolated from human umbilical cord tissue substantially free of blood.

15. The method of claim 10, wherein the population of postpartum-derived cells is administered with at least one other agent.

11. A method of rescuing retinal pigment epithelial (RPE) cell dysfunction in retinal degeneration, the method comprising administering to the eye of a subject a population of postpartum-derived cells, wherein the postpartum-derived cells are isolated from human umbilical cord tissue substantially free of blood, wherein the cell population secretes bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.

13. The method of claim 11, wherein the population of postpartum-derived cells secretes receptor tyrosine kinase trophic factors selected from the group consisting of BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

23. The method of claim 11, wherein the cell population isolated from human umbilical cord tissue substantially free of blood is capable of expansion in culture, has the potential to differentiate into cells of at least a neural phenotype, maintains a normal karyotype upon passaging, and has the following characteristics:

a) potential for 40 population doublings in culture;

b) production of CD10, CD13, CD44, CD73, and CD90;

c) lack of production of CD31, CD34, CD45, CD117, and CD141, and

d) increased expression of genes encoding interleukin 8 and reticulon 1 relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

25. The method of claim 23, wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

12. A method for reducing the loss of photoreceptor cells in retinal degeneration, the method comprising administering to the eye of a subject a population of postpartum-derived cells in an amount effective to reduce the loss of photoreceptor cells, wherein the postpartum-derived cells are isolated from human umbilical cord tissue substantially free of blood, wherein the population of postpartum-derived cells secretes bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.

14. The method of claim 12, wherein the population of postpartum-derived cells secretes receptor tyrosine kinase trophic factors selected from the group consisting of BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

16. A method for reducing the loss of photoreceptor cells in retinal degeneration comprising administering to the eye of a subject a composition comprising a population of postpartum-derived cells, wherein the composition is administered in an amount effective to reduce the loss of photoreceptor cells, wherein the postpartum-derived cells are isolated from human umbilical cord tissue substantially free of blood, wherein postpartum-derived cells secrete bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.

17. The method of claim 16, wherein the population of postpartum-derived cells secretes receptor tyrosine kinase trophic factors selected from the group consisting of BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

18. The method of claim 17, wherein the trophic factors are BDNF, NT3, HGF, PDGF-CC, PDGF-DD, and GDNF.

19. The method of claim 16, wherein the composition is a pharmaceutical composition.

20. The method of claim 19, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.

27. A method for reducing the loss of photoreceptor cells in retinal degeneration comprising administering to the eye of a subject a composition comprising a conditioned medium generated by culturing a population of postpartum-derived cells, wherein the composition is administered in an amount effective to reduce the loss of photoreceptor cells, wherein the postpartum-derived cells are isolated from human umbilical cord tissue substantially free of blood, wherein postpartum-derived cells secrete bridge molecules, and wherein the bridge molecules are selected from MFG-E8, Gas6, TSP-1 and TSP-2.