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.
Claims22
A composition comprising a non-naturally occurring satellite cell, wherein:
- the non-naturally occurring satellite cell has a gene expression profile that is different from the gene expression profile of an endogenous satellite cell;
- the non-naturally occurring satellite cell expresses two or more genes selected from the group consisting of:
- Nr2f1, Dmp1, 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 cell has capacity to repopulate the satellite cell niche;
- and
- the non-naturally occurring satellite cell causes muscle regeneration following transplantation.
An isolated population of non-naturally occurring satellite cells produced by 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 cell expresses two or more genes selected from the group consisting of Nr2f1, Dmp1, Wisp2, Ecm1, Igfbp5, Itgb5, Sdc2, Bgn, 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.
A composition comprising a population of non-naturally occurring satellite cells produced by 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 express two or more genes selected from the group consisting of Nr2f1, Dmp1, 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.