Satellite cells and compositions and methods for producing the same
AssigneePresident and Fellows of Harvard College
InventorsLee L. Rubin, Feodor D. Price
Life of this patent
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Abstract
Disclosed herein are methods for generating satellite cells and compositions including satellite cells.
Claims30
A method for engraftment of non-naturally occurring satellite cells for treating a muscle disorder, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising therapeutically effective amount of an isolated population of non-naturally occurring satellite cells, wherein:
- the non-naturally occurring satellite cells have a gene expression profile that is different from the gene expression profile of an endogenous satellite cell;
- the non-naturally occurring satellite cells express two or more genes selected from the group consisting of:
- Nr2f1, Dmpl, Wisp2/Ccn5, Ecm1, Mgp, Igfbp5, Itgb5, Sdc2 and Bgn, wherein the expression of the two or more genes is upregulated by greater than 2-fold relative to expression by myoblasts and the two or more genes are not expressed in an endogenous satellite cell;
- the non-naturally occurring satellite cells have capacity to repopulate the satellite cell niche;
- and
- the non-naturally occurring satellite cells cause muscle regeneration following transplantation.
A method for treatment of a muscle disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising therapeutically effective amount of an isolated population of non-naturally occurring satellite cells, wherein:
- the non-naturally occurring satellite cells have a gene expression profile that is different from the gene expression profile of an endogenous satellite cell;
- the non-naturally occurring satellite cells express two or more genes selected from the group consisting of:
- Nr2f1, Dmpl, Wisp2/Ccn5, Ecm1, Mgp, Igfbp5, Itgb5, Sdc2 and Bgn, wherein the expression of the two or more genes is upregulated by greater than 2-fold relative to expression by myoblasts and the two or more genes are not expressed in an endogenous satellite cell;
- the non-naturally occurring satellite cells have capacity to repopulate the satellite cell niche;
- and
- the non-naturally occurring satellite cells cause muscle regeneration following transplantation.
A method for treatment of a muscle disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising therapeutically effective amount of an isolated population of non-naturally occurring satellite cells produced according to a method comprising:
- contacting a population of cells comprising myoblasts in spin culture with at least one medium for a time sufficient to induce the dedifferentiation of at least one myoblast in the spin culture into a non-naturally occurring satellite cell, wherein:
- the non-naturally occurring satellite cells produced have a gene expression profile that is different from the gene expression profile of an endogenous satellite cell;
- the non-naturally occurring satellite cells produced express two or more genes selected from the group consisting of:
- Nr2f1, Dmpl, Wisp2/Ccn5, Ecm1, Map, Igfbp5, Itgb5, Sdc2 and Bgn, wherein the expression of the two or more genes is upregulated by greater than 2-fold relative to expression by myoblasts and the two or more genes are not expressed in an endogenous satellite cell.
A method for treatment of a muscle disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising therapeutically effective amount of an isolated population of non-naturally occurring satellite cells produced according to a method comprising:
- contacting a population of cells comprising myoblasts in spin culture with a first medium, wherein the first medium is a myoblast medium, to form an expanded myoblast population;
- contacting the expanded myoblast population with a second medium, wherein the second medium is a spin medium, to form at least one skeletal muscle organoid comprising differentiated and proliferative cells;
- and
- contacting the at least one skeletal muscle organoid in spin culture with a third medium, wherein the third medium is a differentiation medium, for a time sufficient to induce the dedifferentiation of at least one proliferative cell of the skeletal muscle organoid into a non-naturally occurring satellite cell,
- wherein the non-naturally occurring satellite cells produced express two or more genes selected from the group consisting of Nr2f1, Dmpl, Wisp2, Ecm1, and Mgp, and
- wherein the expression of the two or more genes is upregulated by greater than 2-fold relative to expression by myoblasts and the two or more genes are not expressed in an endogenous satellite cell.
Dependencies are inferred from the claim text.