Thymic Epithelial Cells, Exosomes Derived Therefrom, and Methods of Making and Using Same
AssigneeLoyola University of Chicago
InventorPhong Le
Life of this patent
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Abstract
The present disclosure provides engineered thymic epithelial cells and cell lines, as well as extracellular vesicles derived therefrom. The disclosure also provides exosomes that display specific surface proteins, and provides methods for using said materials for treating subjects and for identifying cells.
Claims25
An isolated human thymic epithelial cell comprising at least one expression vector encoding a human Delta-like 4 gene (DLL4), wherein said expression vector is capable of expressing a Delta-like 4 protein.
(canceled)
An isolated human thymic epithelial cell comprising at least one expression vector encoding a human WNT3A gene (WNT3A), wherein said expression vector is capable of expressing a Wnt-3a protein.
(canceled)
The isolated cell of any of the previous claims wherein said cell is a genetically modified cell from cell line TEC84.
(canceled)
An isolated exosome derived from a human thymic epithelial cell, wherein said exosome displays human Delta-like 4 protein on its membrane surface.
An isolated exosome derived from a human thymic epithelial cell, wherein said exosome displays human Wnt-3a protein on its membrane surface.
(canceled)
A method of stimulating production of a T cell from a hematopoietic stem cell, said method comprising the steps of:
- (a) contacting a hematopoietic stem cell expressing a Notch receptor and with an exosome derived from a human thymic epithelial cell, said exosome displaying a human Delta-like 4 protein, wherein said Delta-like 4 protein amino acid sequence is the natural human amino acid sequence or is a fragment, analog or derivative of the natural human amino acid sequence;
- or
- (b) contacting a hematopoietic stem cell with an exosome derived from a human thymic epithelial cell, said exosome displaying a human Wnt-3a protein, wherein said Wnt-3a protein amino acid sequence is the natural human amino acid sequence or is a fragment, analog or derivative of the natural human amino acid sequence;
- or
- (c) both steps (a) and (b).
A method of identifying a subpopulation of hematopoietic stem cells expressing a Notch receptor and capable of developing into T cells, comprising the steps of:
- (a) contacting a hematopoietic stem cell expressing a Notch receptor and with an exosome derived from a human thymic epithelial cell, said exosome displaying a human Delta-like 4 protein on its membrane surface, wherein said Delta-like 4 protein amino acid sequence is the natural human amino acid sequence or is a fragment, analog or derivative of the natural human amino acid sequence;
- (b) contacting the exosome of (a) with an antibody or antigen-binding fragment thereof specific for the Delta-like 4 protein;
- and
- (c) determining the presence of an exosome bound to a hematopoietic stem cell expressing a Notch receptor and an antibody of (b);
- wherein said subpopulation of hematopoietic stem cells expresses one or more cell surface marker selected from the group consisting of CD34, CD7, CD127, CD62L, CCR9, CCR7, and CXCR4, and wherein said subpopulation is from a sample population of hematopoietic stem cells collected from a source selected from the group consisting of umbilical cord blood stem cells, adult peripheral blood hematopoietic stem cells, and bone marrow hematopoietic stem cells.
-28. (canceled)
Dependencies are inferred from the claim text.