ABCB5(+) stem cells for treating ocular disease
Inventors
Frank, Markus H. • Frank, Natasha Y. • Ksander, Bruce • Kolovou, Paraskevi Evi
Assignees
Boston Childrens Hospital • Schepens Eye Research Institute Inc • US Department of Veterans Affairs
Publication Number
US-11129854-B2
Publication Date
2021-09-28
Expiration Date
2034-02-19
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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.
Core Innovation
The invention is directed to the use of ABCB5-positive (ABCB5(+)) stem cells for treatment of ocular conditions such as corneal and retinal diseases. ABCB5 is expressed in stem cells of the eye and these stem cells are essential for normal eye development. When administered to subjects with ocular wounds, these ABCB5(+) stem cells promote ocular cell regeneration, specifically corneal regeneration by limbal stem cells and retinal regeneration by retinal pigment epithelium (RPE) stem cells.
The invention includes methods of isolating ABCB5(+) limbal stem cells from mixed ocular cell populations, selecting or producing ocular grafts enriched in ABCB5(+) stem cells for transplantation, and administering these cells or grafts to subjects in need to treat ocular conditions. ABCB5 expression is employed as a marker for prospective isolation of limbal stem cells, which had not been available previously, thus enhancing therapeutic success for conditions such as limbal stem cell deficiency (LSCD).
The problem addressed is the lack of a molecular marker to prospectively identify and enrich limbal stem cells critical for corneal regeneration and repair. Limbal stem cell deficiency leads to blindness, and prior to this invention, treatments depended on grafting limbal tissue with variable stem cell content. The invention overcomes this by identifying ABCB5 as a functional marker to isolate stem cells capable of effective regeneration, thereby improving transplantation outcomes.
Claims Coverage
The patent contains one independent claim directed to a method of isolating limbal stem cells characterized by ABCB5 expression from a mixed population of ocular cells, encompassing various antibody-based isolation techniques and sources.
Isolation of ABCB5(+) limbal stem cells from mixed ocular cells
A method comprising providing a mixed population of ocular cells and isolating ABCB5(+) limbal stem cells from this population.
Use of antibodies selectively binding ABCB5 for isolation
The method includes contacting the mixed ocular cell population with antibodies or antibody fragments that selectively bind to human ABCB5 to isolate the ABCB5(+) limbal stem cells.
Sourcing ocular cells from basal limbal epithelium
The ocular cells provided for the isolation method are obtained from the basal limbal epithelium of an eye.
Employment of diverse ABCB5-binding molecules
The method utilizes binding molecules selected from monoclonal, polyclonal, human, chimeric, humanized antibodies, and various antibody fragments to isolate ABCB5(+) limbal stem cells.
The claims cover the novel use of selective binding to ABCB5 for prospective isolation of limbal stem cells from ocular tissues, specifically involving antibody-mediated separation from basal limbal epithelium cells, which enables enrichment of stem cells for therapeutic use.
Stated Advantages
Provides a molecular marker (ABCB5) enabling prospective identification and enrichment of limbal stem cells, enhancing the success of limbal stem cell transplantation.
ABCB5(+) stem cells are essential for normal corneal development, regeneration, and repair, supporting improved therapeutic outcomes for corneal diseases.
Isolation of ABCB5(+) stem cells permits the production of ocular grafts with enriched stem cell populations, increasing graft efficacy and reducing graft failure.
Identification of ABCB5 function in maintaining limbal stem cell quiescence and survival offers insights into corneal pathology and regeneration mechanisms.
Documented Applications
Treatment of ocular conditions including corneal diseases such as blindness due to limbal stem cell deficiency (LSCD).
Treatment of retinal diseases such as macular degeneration and retinitis pigmentosa.
Use in ocular wounds to promote ocular cell regeneration and prevent scarring leading to vision loss.
Preparation of ocular grafts containing ABCB5(+) stem cells for transplantation to restore damaged corneal or retinal tissue.
Expansion of isolated ABCB5(+) stem cells ex vivo for therapeutic administration.
Producing artificial grafts such as artificial corneas by seeding isolated ABCB5(+) stem cells on acellular collagen or biocompatible substrates.
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