Compositions And Methods For Cell Based Retinal Therapies
The invention relates to pharmaceutical compositions comprising trophic factors, methods to decrease the degeneration of a retina, methods of treating ocular degenerative diseases and methods to select cells for transplantation.
1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least two biologically active trophic factors selected from the group consisting of LIF, bFGF, HB-EGF, VEGF-A, NGF, BDNF, CNTF, PEDF, IGFBP-3, isoform 1 of semaphoring-3B, TGF-β and HGF.
2 . The pharmaceutical composition of claim 1 wherein, the selected biologically active trophic factors are HGF and PEDF.
3 . The pharmaceutical composition of claim 1 comprising LIF, bFGF, HB-EGF, VEGF-A, NGF, BDNF, CNTF, HGF and PEDF.
4 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier is capable of sustained release delivery of said factors.
5 . A method to decrease the degeneration of a retina associated with an ocular condition in a subject in need thereof comprising administration to said subject an effective amount of the pharmaceutical composition of claim 1 .
6 . The method of claim 5 , wherein the pharmaceutical composition is administered by intraocular administration.
7 . The method of claim 5 , wherein said ocular condition is selected from the group consisting of age-related macular degeneration, retinitis pigmentosa, glaucoma, optic atrophy, ocular inflammation, retinopathy, diabetic retinopathy, retinal ganglion cell dysfunction, and retinal detachment.
8 . A method to select a group of cells that secrete factors that decrease the degeneration of a retina comprising:
a. isolating medium from a group of cultured cells;
b. culturing a degenerating animal retina with said isolated medium;
c. determining the degeneration of the retina; and
d. comparing the level of the degeneration of the retina to a standard;
wherein the group of cells are selected if said isolated medium decreased the degeneration of the retina compared to the standard.
9 . The method of claim 8 , where in the group of cells are stem cells capable of differentiating to retinal pigment epithelial cells, or fetal retinal pigment epithelial cells.
10 . The method of claim 8 , wherein the determining step is conducted by performing a cytotoxicity assay and/or an apoptotic assay.
11 . The method of claim 8 , wherein the standard is the level of the degeneration of a retina cultured in non-conditioned medium.
12 . The method of claim 8 , wherein the cells are human cells
13 . The method of claim 8 , wherein the group of cultured cells is cultured in a solid support.
14 . The method of claim 8 , wherein the degenerating retina is cultured in a solid support.
15 . The method of claim 8 , wherein the animal retina is a human retina or a porcine retina.
16 . Conditioned medium isolated from fetal retinal pigment epithelial cells cultured in medium in a solid support, wherein said medium is isolated after said cells have been passaged from 2 to 6 passages and within 7 days of said passage.
17 . A method of identifying cells for transplantation to a subject having an ocular condition comprising:
a. isolating medium from a group of cultured cells;
b. culturing a degenerating animal retina with said isolated medium;
c. determining the degeneration of the retina; and
d. comparing the level of the degeneration of the retina to a standard;
wherein the group of cells are selected if said isolated medium decreased the degeneration of the retina compared to a standard.
18 . The method of claim 17 , wherein said group of cells are stem cells isolated from the subject.
19 . The method of claim 17 , wherein the cells are human cells
20 . The method of claim 17 wherein the group of cultured cells is cultured in a solid support.
21 . The method of claim 17 wherein the degenerating retina is cultured in a solid support.
22 . The method of claim 17 wherein the animal retina is a human retina or a porcine retina.
23 . A kit for identifying an agent that decreases degeneration of a retina wherein the kit comprises an explant culture of full thickness animal retina.
24 . The kit of claim 23 wherein the retina is a human or a porcine retina.
25 . The kit of claim 23 further comprising reagents for performing an assay for measuring retinal degradation.