Induced pluripotent cell-derived oligodendrocyte progenitor cells for the treatment of myelin disorders
The present disclosure relates to a preparation of CD140a/PDGFRα positive cells that comprises oligodendrocyte progenitor cells co-expressing OLIG2 and CD140a/PDGFRα. The preparation of cells is derived from pluripotent cells that were derived from skin cells, fibroblasts, umbilical cord blood, peripheral blood, bone marrow, or other somatic cells. The cell preparation has an in vivo myelination efficiency that is equal to or greater than the in vivo myelination efficiency of a preparation of A2B5 + /PSA-NCAM − sorted fetal human tissue derived oligodendrocyte progenitor cells. Methods of making, isolating and using the disclosed cell preparation are also described.
1. A population of cells derived from human induced pluripotent stem cells, wherein greater than 30% of said population comprises human oligodendrocyte progenitor cells, wherein said human oligodendrocyte progenitor cells in the population co-express oligodendrocyte transcription factor 2 (OLIG2) and CD140a/platelet derived growth factor receptor-α (PDGFRα), and wherein less than 12% of the cells of the population are oligodendrocytes expressing the surface lipid sulfatide recognized by the O4 antibody.
2. The population of claim 1 , wherein the oligodendrocyte progenitor cells of the population further express SRY Box 10 (SOX10), CD9, or a combination thereof.
3. The population of claim 1 , wherein said population of cells does not contain microtubule-associated protein 2 (MAP2) expressing neurons.
4. The population of claim 1 , wherein said population contains less than 1% residual pluripotent cells.
5. The population of claim 1 , wherein said population has an in vivo myelination efficiency that is greater than the in vivo myelination efficiency of a population of A2B5 + /polysialylated-neural cell adhesion molecule (PSA-NCAM − )sorted fetal human tissue derived oligodendrocyte progenitor cells.
6. The population of claim 1 , wherein said population is capable of achieving an in vivo myelination density upon engraftment which is greater than that achieveable with a population of A2B5 + /PSA-NCAM − sorted fetal human tissue derived oligodendrocyte progenitor cells.
7. The population of claim 1 , wherein said population is capable upon engraftment of achieving improved survival in a myelination deficient mammal compared to that achieveable with a population of A2B5 + /PSA-NCAM − sorted fetal human tissue derived oligodendrocyte progenitor cells.
8. The population of claim 1 , wherein 4%-12% of the cells of the population are oligodendrocytes expressing the surface lipid sulfatide recognized by the O4 antibody.
9. The population of claim 1 , wherein greater than 50% of said population comprises human oligodendrocyte progenitor cells.