US2022118024A1PendingUtilityA1

Abcb5(+) stem cells for treating ocular disease

69
Assignee: US VETERANS AFFAIRSPriority: Feb 19, 2013Filed: Sep 27, 2021Published: Apr 21, 2022
Est. expiryFeb 19, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Markus FrankNatasha Y. FrankBruce KsanderParaskevi Evi Kolovou
C12N 5/0621A61L 27/3834C12N 2501/604A61P 27/02A61L 27/3839A61L 2430/16C12N 2501/603C12N 2500/02A61K 35/30C12N 2501/602C12N 5/0696C12N 5/0623A61K 9/0051C12N 5/0668
69
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Claims

Abstract

Various aspects and embodiments of the present invention are directed to methods of treating a subject having an ocular condition, methods of isolating ocular stem cells, methods of selecting and/or producing ocular grafts for transplantation, and methods of promoting ocular cell regeneration as well as to grafts and preparations containing isolated ocular stem cells characterized by the expression of ABCB5 on their cell surface.

Claims

exact text as granted — not AI-modified
1 . A method of treating a subject having an ocular condition, comprising administering to the subject isolated ABCB5(+) ocular stem cells in an amount effective to regenerate ocular cells in the subject. 
     
     
         2 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered as an ocular graft, wherein the ocular graft comprises an artificial cornea comprised of the ABCB5(+) ocular stem cells. 
     
     
         9 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are allogeneic stem cells. 
     
     
         10 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are syngeneic stem cells. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are ABCB5(+) limbal stem cells. 
     
     
         13 - 30 . (canceled) 
     
     
         31 . A method of producing an ocular graft for transplantation to a subject, comprising seeding a substrate with isolated ocular ABCB5(+) stem cells to produce the ocular graft. 
     
     
         32 . The method of  claim 31 , wherein the isolated ABCB5(+) ocular stem cells are allogeneic stem cells. 
     
     
         33 - 38 . (canceled) 
     
     
         39 . The method of  claim 31 , wherein the substrate comprises fibrin gel, amniotic membrane, aminoglycans, or a combination thereof. 
     
     
         40 . An ocular graft enriched with isolated ABCB5(+) stem cells for transplantation in a subject. 
     
     
         41 . The ocular graft of  claim 40 , wherein the isolated ABCB5(+) stem cells are allogeneic stem cells. 
     
     
         42 . The ocular graft of  claim 40 , wherein the isolated ABCB5(+) stem cells are syngeneic stem cells. 
     
     
         43 . The ocular graft of  claim 40 , wherein the isolated ABCB5(+) stem cells are ABCB5(+) ocular stem cells. 
     
     
         44 - 56 . (canceled) 
     
     
         57 . An in vitro substrate, comprising an artificial cornea comprised of ABCB5(+) ocular stem cells. 
     
     
         58 . The substrate of  claim 57 , wherein the ABCB5(+) ocular stem cells are limbal stem cells. 
     
     
         59 . The substrate of  claim 57 , wherein the ABCB5(+) ocular stem cells are retinal stem cells. 
     
     
         60 . The substrate of  claim 57 , wherein the ABCB5(+) ocular stem cells are human eye cells. 
     
     
         61 . The substrate of  claim 57 , wherein the ABCB5(+) ocular stem cells are central corneal cells. 
     
     
         62 . The substrate of  claim 57 , wherein at least 1.0% of the total cell population is ABCB5(+). 
     
     
         63 . The substrate of  claim 57 , wherein at least 3.0% of the total cell population is ABCB5(+). 
     
     
         64 . substrate of  claim 57 , wherein at least 5.0% of the total cell population is ABCB5(+). 
     
     
         65 . substrate of  claim 57 , wherein at least 10.0% of the total cell population is ABCB5(+). 
     
     
         66 . substrate of  claim 57 , wherein the in vitro substrate comprises acellular collagen. 
     
     
         67 . substrate of  claim 57 , wherein the in vitro substrate is in a culture medium. 
     
     
         68 . substrate of  claim 67 , wherein the culture medium comprises salts, buffers, and amino acids. 
     
     
         69 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered in a cell population and at least 1.0% of the total cell population is ABCB5(+). 
     
     
         70 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered in a cell population and at least 3.0% of the total cell population is ABCB5(+). 
     
     
         71 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered in a cell population and at least 50.0% of the total cell population is ABCB5(+). 
     
     
         72 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered in a cell population and at least 90.0% of the total cell population is ABCB5(+). 
     
     
         73 . The method of  claim 1 , wherein the isolated ABCB5(+) ocular stem cells are administered in a cell population and at least 95.0% of the total cell population is ABCB5(+). 
     
     
         74 . The method of  claim 31 , wherein the ABCB5+ ocular stem cells are separated from other cells with an anti-ABCB5 antibody. 
     
     
         75 . The method of  claim 31 , wherein the ABCB5+ ocular stem cells are separated from other cells with flow cytometry.

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