Medium, methods, cells and secreted factors for stem cell culture and therapy
Inventors
Betancourt, Aline M. • Waterman, Ruth S. • ISETT, Thomas F.
Assignees
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Publication Number
US-12553033-B2
Publication Date
2026-02-17
Expiration Date
Abstract
Described herein are methods and culture medium, useful for inducing polarization in multipotent stem cells. Additionally, described herein are multipotent cells produced by the methods and culture medium of this disclosure that are useful therapeutic agents. Also described herein are extracellular vesicles and factors secreted by multipotent cells that are produced by the methods and culture medium of this disclosure that are useful as therapeutic agents.
Core Innovation
The disclosure describes a method for treating an inflammatory or autoimmune condition in a subject by administering a therapeutically effective amount of an immunologically polarized multipotent stem cell population. The immunologically polarized multipotent stem cell population is made by culturing a population of multipotent stem cells in a medium comprising a Toll-like receptor 3 (TLR3) ligand and an agent selected from acetylcholine, glutamate, and lipoxin A4.
The disclosure further characterizes immunologically polarized multipotent stem cells as immunologically distinct type 1 (pro-inflammatory) or type 2 (anti-inflammatory) phenotypes. The polarization is generated using Toll-like receptor signaling plus a second inducing agent, and the resulting polarized cells are associated with distinct secretomes and extracellular vesicles.
The disclosure reports that different TLR and second inducing agent combinations produce different biological outputs, including changes in CXCL9 mRNA and TNFSF10 (TRAIL) mRNA, and differences in secreted cytokines, chemokines, miRNA profiles, and extracellular vesicle protein signatures between the polarized populations. It describes therapeutic use not only of the polarized cells, but also of secreted products including conditioned medium and extracellular vesicles such as exosomes.
Claims Coverage
The independent claims cover 1 inventive feature: methods for treating inflammatory or autoimmune conditions by administering immunologically polarized multipotent stem cell populations produced by culturing multipotent stem cells in a medium containing a TLR3 ligand plus a second inducing agent selected from acetylcholine, glutamate, and lipoxin A4 with specified minimum concentrations.
Treating an inflammatory or autoimmune condition by administering TLR3/second-agent polarized multipotent stem cells
Administering a therapeutically effective amount of an immunologically polarized multipotent stem cell population to treat an inflammatory or autoimmune condition in a subject, where the immunologically polarized multipotent stem cell population is made by culturing multipotent stem cells in a medium comprising a Toll-like receptor 3 (TLR3) ligand and an agent selected from acetylcholine, glutamate, and lipoxin A4.
Claim coverage centers on producing immunologically polarized multipotent stem cells using TLR3 ligand plus a second inducing agent selected from acetylcholine, glutamate, and lipoxin A4 at specified minimum concentrations, and on administering the resulting polarized multipotent stem cell population for treatment of an inflammatory or autoimmune condition.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating an inflammatory or autoimmune condition in a subject by administering a therapeutically effective amount of an immunologically polarized multipotent stem cell population made by culturing with a TLR3 ligand and a selected agent.
Rheumatoid arthritis, diabetic neuropathy, Crohn's disease, acute lung injury, multiple sclerosis, acute optic neuritis, or Krabbe disease, as selected inflammatory or autoimmune conditions for the method.
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