Induction medium and methods for stem cell culture and therapy
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Publication Number
US-10273449-B2
Publication Date
2019-04-30
Expiration Date
Abstract
Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy.
Core Innovation
The disclosure relates to a cell culture comprising multipotent stem cells and a culture medium that includes a Toll-like receptor-4 ligand and erythropoietin, where the cell culture is present in a hypoxic environment. The approach provides a culture induction medium that combines TLR ligand activity with erythropoietin and hypoxia, including hypoxia generated by hypoxia mimetics.
The disclosure connects specific TLR priming with defined multipotent stem cell phenotypes. TLR3 priming is associated with an anti-inflammatory or immunosuppressive MSC2 phenotype, while TLR4 priming is associated with a pro-immune inflammatory or anti-tumor MSC1 phenotype.
The disclosure further describes culture implementations in which conditioned medium is used and culture is performed in hermetically-sealed culture vessel formats. It states that the induction and priming enable uniform, predictable ex vivo cell phenotypes and improved preclinical outcomes, and it lists therapeutic utility for inflammatory and immune disorders.
Claims Coverage
The document contains one independent claim directed to a cell culture, with multiple dependent refinements that add specific identities and quantitative conditions for the TLR4 ligand, hypoxic environment, and culture medium composition. The independent claim includes three core inventive elements: multipotent stem cells, a TLR4 ligand plus erythropoietin in the culture medium, and maintenance of the culture in a hypoxic environment.
Multipotent stem cells with TLR4 ligand and erythropoietin
A cell culture comprising multipotent stem cells and a culture medium comprising a Toll-like receptor-4 ligand and erythropoietin.
TLR4 ligand concentration range
The culture medium includes a TLR4 ligand at a concentration from about 100 pg/ml to about 10 μg/ml.
Hypoxic environment maintenance
The cell culture is present in a hypoxic environment.
TLR4 ligand selection as lipopolysaccharide
The TLR4 ligand is lipopolysaccharide (LPS).
Hypoxia via hypoxia mimetic
The hypoxic environment is generated by the presence of a hypoxia mimetic in the culture medium.
Oxygen concentration range for hypoxia
The cell culture is maintained in a hypoxic environment with an oxygen level of 0.5% to 2.0%.
Serum-free medium requirement
The culture medium is serum-free.
Overall, claim coverage centers on culturing multipotent stem cells in a medium containing a TLR4 ligand within a specified concentration range and erythropoietin, while maintaining the culture in a hypoxic environment. Dependent refinements further specify that the TLR4 ligand can be LPS, that hypoxia can be generated using a hypoxia mimetic and an oxygen level range, and that the medium can be serum-free.
Stated Advantages
Uniform, predictable ex vivo cell phenotypes.
Improved preclinical outcomes.
Therapeutic utility for inflammatory and immune disorders.
Documented Applications
Therapeutic utility for inflammatory/immune disorders (cell-based therapy / cellular therapy medicament context).
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