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US 11,111,375 B2Granted
Compositions and methods for generating oligodendrocyte precursors
AssigneeThe Regents of the University of California
InventorsGonçalo Rodrigues, David V. Schaffer
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Abstract
The present disclosure provides a three-dimensional culture system comprising a biocompatible polymer and a combination of factors in an amount effective to induce differentiation of oligodendrocyte precursors and/or oligodendrocytes from pluripotent stem cells. The present disclosure provides methods of generating oligodendrocyte precursors and/or oligodendrocytes using a three-dimensional culture system of the present disclosure. The present disclosure provides methods to treat neurological diseases and demyelinating diseases.
Claims13
A three-dimensional culture system comprising:
- a) biocompatible thermoresponsive polymer that forms a hydrogel at 37° C.;
- and
- b) a combination of factors that promote differentiation of oligodendrocyte precursors from pluripotent stem cells in 20 days or less, wherein the combination of factors consists of a Sonic hedgehog (Shh) signaling pathway agonist and retinoic acid (RA);
- and
- wherein the thermoresponsive polymer comprises:
- an N-isopropylacrylamide co-monomer;
- an alkyl [meth]acryl[ate/amide] co-monomer, wherein the alkyl is a lower alkyl group;
- a PEG acrylamide co-monomer;
- and
- a modifying acryl[ate/amide] co-monomer comprising a linked functional group or a linked modifying agent,
- wherein the thermoresponsive polymer is described by formula (II):
- wherein:
- a, b, c and d are molar fractions of the co-monomers, wherein a >0.8, 0.1>b>0, and 0.2>c>0;
- PEGn is a polyethylglycol polymer;
- Z2 is a functional group or a linked modifying agent;
- L is a linker;
- R1 is a lower alkyl;
- G1 and G2 are each independently selected from a polymer segment, a terminal group, a linker and a linked modifying agent.
15 more elements
Dependencies are inferred from the claim text.