Trabecular Meshwork Stem Cells

Abstract

Provided herein are isolated populations of multipotent stem cells capable of differentiating into trabecular meshwork (TM) cells, methods of obtaining an isolated population of TM cells, and isolated populations of TM cells obtained therefrom. Compositions, kits, and devices comprising the isolated populations of multipotent stem cells or TM cells are also provided herein. Further provided are methods of using the compositions, kits, and devices for decreasing intraocular pressure in an eye, increasing cell density in a trabecular meshwork of an eye, increasing outflow of aqueous humor from an eye, or treating or preventing a medical condition in a subject.

1 . An isolated population of multipotent stem cells which are capable of differentiating into trabecular meshwork (TM) cells. 
     
     
         2 . The isolated population of  claim 1 , comprising multipotent stem cells isolated from a TM. 
     
     
         3 . The isolated population of  claim 2 , wherein the TM is a TM of a mammal. 
     
     
         4 . The isolated population of  claim 3 , wherein the mammal is a human. 
     
     
         5 . The isolated population of  claim 2 , wherein the TM is obtained from a tissue bank. 
     
     
         6 . The isolated population of  claim 2 , comprising multipotent stem cells isolated from a filtering region of the TM. 
     
     
         7 . The isolated population of  claim 6 , comprising multipotent stem cells isolated from a non-filtering region of the TM. 
     
     
         8 . The isolated population of  claim 1 , wherein at least 90% of the cells of the population express a stem cell marker selected from the group consisting of ABCG2, Pax6, Nestin, AnkyrinG, Mucin1, CD73, CD90, CD166, Bmi-1, Oct4, CD 117, Notch1, KLF4, and a combination thereof. 
     
     
         9 . The isolated population of  claim 8 , wherein at least 90% of the cells of the population express AnkyrinG and Mucin1. 
     
     
         10 . The isolated population of  claim 1 , wherein the multipotent stem cells express at a reduced level, as compared to TM cells, a TM cell marker selected from the group consisting of MGP, AQP1, CHI3L1, NCAM, TIMP3, and a combination thereof. 
     
     
         11 . The isolated population of  claim 1 , wherein the multipotent stem cells are capable of differentiating into TM cells, corneal keratocytes, neural cells, and adipocytes. 
     
     
         12 . The isolated population of  claim 1 , wherein the multipotent stem cells are capable of differentiating into phagocytic TM cells. 
     
     
         13 . A method of obtaining an isolated population of TM cells, comprising obtaining an isolated population of multipotent stem cells and culturing the isolated population of multipotent stem cells in a medium comprising factors present in fetal bovine serum, aqueous humor, or in both fetal bovine serum and aqueous humor, to induce differentiation of the multipotent stem cells into TM cells. 
     
     
         14 . The method of  claim 13 , wherein the isolated population of multipotent stem cells is in accordance with  claims 1 . 
     
     
         15 . The method of  claim 13 , wherein the isolated population of multipotent stem cells is obtained by side population cell sorting of cells of a trabecular meshwork. 
     
     
         16 . The method of  claim 13 , wherein the isolated population of multipotent stem cells is obtained by clonal expansion of cells of a trabecular meshwork. 
     
     
         17 . The method of  claim 13 , wherein the isolated population of multipotent stem cells is obtained by selective expansion of stem cells of a trabecular meshwork. 
     
     
         18 . The method of  claim 13 , wherein the isolated population of multipotent stem cells are cultured in a medium comprising aqueous humor or fetal bovine serum. 
     
     
         19 . An isolated population of TM cells obtained through the method of  claim 13 . 
     
     
         20 . The isolated population of TM cells of  claim 19 , wherein the TM cells express at an increased level, as compared to the multipotent stem cells from which the TM cells originated, a TM cell marker selected from the group consisting of MGP, AQP1, CHI3L1, NCAM, and TIMP3, and a combination thereof. 
     
     
         21 . The isolated population of TM cells of  claim 19 , wherein the TM cells are phagocytic TM cells. 
     
     
         22 . A composition comprising the isolated population of multipotent stem cells of  claim 1 , and a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
         23 . A composition comprising the isolated population of TM cells of  claim 19 , and a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
         24 . The composition of  claim 22 , further comprising a medium comprising factors present in fetal bovine serum, aqueous humor, or in both fetal bovine serum and aqueous humor 
     
     
         25 . The composition of  claim 24 , wherein the cells are from a human and the aqueous humor is from a non-human. 
     
     
         26 . The composition of  claim 22 , wherein the cells are in solution. 
     
     
         27 . The composition of  claim 22 , wherein the cells are cryopreserved. 
     
     
         28 . The composition of  claim 22 , formulated for administration to a subject by implantation or injection. 
     
     
         29 . The composition of  claim 22 , formulated for sustained, continuous release. 
     
     
         30 . The composition of  claim 22 , wherein the cells are in a matrix, capsule, or gel. 
     
     
         31 . A method of decreasing intraocular pressure in an eye, comprising administering to a subject in need of decreasing intraocular pressure in the eye the composition of  claim 22 , in an amount effective to decrease the intraocular pressure in the eye. 
     
     
         32 . A method of increasing cell density in a trabecular meshwork {TM} of an eye, comprising administering to a subject in need of increasing cell density in the trabecular meshwork of the eye the composition of  claim 22 , in an amount effective to increase cell density in the TM. 
     
     
         33 . A method of increasing outflow of aqueous humor from an eye, comprising administering to a subject in need of increasing outflow of aqueous humor from the eye the composition of  claim 22 , in an amount effective to increase the outflow. 
     
     
         34 . A method of treating or preventing a medical condition caused by or associated with decreased cell density in a trabecular meshwork of an eye, increased intraocular pressure in an eye, decreased outflow of aqueous humor from the eye, or a combination thereof, comprising administering to a subject with the medical condition the composition of  claim 22 , in an amount effective to treat the medical condition. 
     
     
         35 . The method of  claim 34 , wherein the medical condition is glaucoma. 
     
     
         36 . The method of  claim 31 , wherein the composition is injected into the eye of the subject. 
     
     
         37 . The method of  claim 36 , wherein the composition is injected into the TM or Schlemm's canal of the eye. 
     
     
         38 . The method of  claim 31 , wherein the composition is injected into the blood stream of the subject. 
     
     
         39 . The method of  claim 31 , wherein the cells are in a matrix or capsule and the matrix or capsule is implanted into the anterior chamber, trabecular meshwork, or Schlemm's canal of the subject. 
     
     
         40 . A kit comprising the composition of  claim 22  and instructions for use. 
     
     
         41 . The kit of  claim 40 , comprising a device for administration of the composition to a subject. 
     
     
         42 . The kit of  claim 40 , comprising instructions for administration of the composition to a subject. 
     
     
         43 . A device comprising the composition of  claim 22 . 
     
     
         44 . The device of  claim 41 , which is a syringe, a matrix, a capsule, or an intravenous bag.