Methods for producing enriched populations of human retinal pigment epithelium cells

Patent metadata

Field	Value
Publication number	US-9649340-B2
Application number	US-85786610-A
Country	US
Kind code	B2
Filing date	Aug 17, 2010
Priority date	Jan 23, 2004
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

First claim

We claim:

1. A method of treating retinal disease or condition in an human subject, comprising transplanting into the eye of said subject a composition comprising an allogeneic human pigmented cell population comprising bestrophin+/CRALBP+ cells obtained by in vitro differentiation of human pluripotent cells that express Oct-4, alkaline phosphatase, SSEA-3, SSEA-4, TRA-I-60, and TRA-I-81, wherein the human pigmented cell population has a normal karyotype.

2. The method of claim 1 , wherein said human pigmented cell population comprises cells that are bestrophin+, CRALBP+, PEDF+, and express RPE65.

3. The method of claim 1 , wherein said human pigmented cell population comprises cells that are Pax6+.

4. The method of claim 1 , wherein said retinal disease or condition is a disease of retinal degeneration.

5. The method of claim 1 , wherein the retinal disease or condition comprises pathologic myopia, retinitis pigmentosa, RPE detachment, retinal dysplasia, retinal atrophy, retinopathy, macular dystrophy, cone dystrophy, cone-rod dystrophy, Malattia Leventinese, Doyne honeycomb dystrophy, Sorsby's dystrophy, Stargardt disease, pattern/butterfly dystrophies, Best vitelliform dystrophy, North Carolina dystrophy, central areolar choroidal dystrophy, angioid streaks, or a toxic maculopathy.

6. The method of claim 1 , which comprises transplantation of the human pigmented cell population by vitrectomy surgery into the subretinal space of the eye of said human subject.

7. The method of claim 1 , wherein said human pigmented cell population is transplanted into the eye of said human subject in a suspension format or on a substrate or matrix having said human pigmented cell population disposed thereon.

8. The method of claim 1 , wherein the retinal disease or condition is macular degeneration.

9. The method of claim 1 , wherein the retinal disease or condition is Stargardt disease.

10. The method of claim 1 , wherein the retinal disease or condition is age-related macular degeneration.

11. The method of claim 1 , wherein the retinal disease or condition is retinitis pigmentosa.

12. The method of claim 1 , wherein said human pigmented cell population comprises pigmented cells that exhibit a cobblestone, polygonal appearance characteristic of epithelial cells in culture.

13. The method of claim 1 , wherein said human pigmented cell population is prepared by a method comprising:
a) allowing hES cell cultures to overgrow on MEF and form a thick multilayer of cells, or forming an embryoid body (EB) from hES cells;
b) culturing the multilayer of cells or EB for a sufficient time for the appearance of pigmented cells; and
c) isolating and culturing the pigmented cells from the resultant cell cultures, thereby obtaining a human pigmented cell population comprising CRALBP+/bestrophin+cells.

14. The method of claim 13 , wherein said culturing in step (b) comprises culturing the hES cells in a medium lacking exogenously added FGF, lacking exogenously added LIF and lacking exogenously added PLASMANATE® (an aqueous solution containing 5 g plasma proteins per 100 mL, buffered with sodium carbonate and stabilized with 0.005 M sodium caprylate and 0.004 M acetyltryptophan, said plasma proteins comprising approximately 88% normal human albumin, 12% alpha and beta globulins, and not more than 1% gamma globulin, and containing sodium 145 mEq/L, potassium 0.25 mEq/L, and chloride 100 mEq/L).

15. The method of claim 13 , wherein the duration of culturing in step (b) is at least 6 weeks.

16. The method of claim 13 , wherein the duration of culturing in step (b) is between about 6 weeks and about 8 weeks.

17. The method of claim 13 , wherein the duration of culturing in step (b) is between about 3 months and about 5 months.

18. The method of claim 1 , wherein the method restores visual acuity in the subject.

19. The method of claim 18 , wherein visual acuity is restored to a moderate level.

Assignees

• Klimanskaya Irina V
• Lanza Robert P
• Astellas Inst For Regenerative Medicine

Inventors

• Klimanskaya Irina V
• Lanza Robert P

Classifications

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P27/00

  Drugs for disorders of the senses · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title