Treatment of Ocular Conditions Using Progenitor Cells

Patent metadata

Field	Value
Publication number	US-2016158293-A1
Application number	US-201514960055-A
Country	US
Kind code	A1
Filing date	Dec 4, 2015
Priority date	Dec 5, 2014
Publication date	Jun 9, 2016
Grant date	—

Abstract

Methods and compositions for treating ophthalmic disease, promoting development of functional neuronal synapses and improving neuronal outgrowth using progenitor cells, such as postpartum-derived cells, and conditioned media from the cells, are disclosed. Trophic factors and other agents secreted by the cells that promote synapse formation and neuronal growth are also disclosed.

First claim

We claim:

1 . A method of administering a population of postpartum-derived cells to the eye of a subject with retinal degeneration, wherein the cell population is a homogenous population of human umbilical cord tissue-derived cells, wherein the human umbilical cord tissue-derived cells are isolated from human umbilical cord tissue substantially free of blood, wherein the population of cells secretes at least one synaptogenic factor, and wherein the synaptogenic factor is selected from TSP-1, TSP-2, and TSP-4.

2 . A method of inducing synaptogenesis or neurite outgrowth in retinal neurons comprising administering a homogenouse population of human umbilical cord tissue-derived cells to the eye of a subject, wherein the cell population is isolated from human umbilical cord tissue substantially free of blood, wherein the population of human umbilical cord tissue-derived cells secretes at least one synaptogenic factor, and wherein the synaptogenic factor is selected from TSP-1, TSP-2, and TSP-4.

3 . A method of developing functional synapses in retinal neurons in a subject with retinal degeneration comprising administering a composition to the eye of the subject comprising a homogeneous population of human umbilical cord tissue-derived cells, wherein the cell population is isolated from human umbilical cord tissue substantially free of blood, wherein the population of human umbilical cord tissue-derived cells secretes at least one synaptogenic factor, and wherein the synaptogenic factor is selected from TSP-1, TSP-2, and TSP-4.

4 . A method of administering a population of human umbilical cord tissue-derived cells to the eye of a subject with retinal degeneration, wherein the cell population is isolated from human umbilical cord tissue substantially free of blood, wherein the population of human umbilical cord tissue-derived cells secretes at least one synaptogenic factor, and wherein the synaptogenic factor is selected from TSP-1, TSP-2, and TSP-4.

5 . The method of claim 1 , 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.

6 . The method of claim 5 , wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

7 . The method of claim 2 , wherein the retinal neurons are selected from the group consisting of retinal ganglion cells, photoreceptors (rods and cones), retina amicrine cells, horizontal cells or bipolar cells.

8 . 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.

9 . The method of claim 3 , wherein the composition is a pharmaceutical composition.

10 . The method of claim 9 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.

11 . The method of claim 2 , 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.

12 . The method of claim 11 , wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

13 . The method of claim 2 , wherein administration to the eye is selected from administration to the interior of an eye or administration behind the eye.

14 . 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.

15 . The method of claim 14 , wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

16 . The method of claim 3 , wherein the retinal neurons are selected from the group consisting of retinal ganglion cells, photoreceptors (rods and cones), retina amicrine cells, horizontal cells or bipolar cells.

17 . The method of claim 3 , wherein administration to the eye is selected from administration to the interior of an eye or administration behind the eye.

18 . The method of claim 4 , 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.

19 . The method of claim 18 , wherein the cell population is positive for HLA-A,B,C, and negative for HLA-DR,DP,DQ.

20 . The method of any of claim 4 , wherein administration to the eye is selected from administration to the interior of an eye or administration behind the eye.

Assignees

• Janssen Biotech Inc

Inventors

• Harris Ian R
• Dejneka Nadine

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• C12N2502/025

  extra-embryonic cells, e.g. amniotic epithelium, placental cells, Wharton's jelly · CPC title

• C12N5/062

  Sensory transducers, e.g. photoreceptors; Sensory neurons, e.g. for hearing, taste, smell, pH, touch, temperature, pain · CPC title

• A61K35/51 Primary

  Umbilical cord; Umbilical cord blood; Umbilical stem cells · CPC title

• A61K9/0051

  Ocular inserts or implants · CPC title