Stimulation of mesenchymal stem cell therapeutic activities by T regulatory cells
Inventors
Ichim, Thomas E. • Ramos, Famela • Veltmeyer, James • Dixon, Timothy G. • Lin, Feng • O'Connor, Kalina
Assignees
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Publication Number
US-12011462-B2
Publication Date
2024-06-18
Expiration Date
Abstract
Disclosed are novel means of enhancing mesenchymal stem cell regenerative activities including, intra alia, production from pulmonary leakage and suppression of scar tissue formation by co-administration with T regulatory cells. In some embodiments the invention provides an interaction between T regulatory cells and mesenchymal stem cells in which T regulatory cells stimulate upregulation of mesenchymal stem cell activity in a GITR dependent manner.
Core Innovation
The invention relates to a stem-cell therapy for inhibiting lung inflammation by administering a population of T regulatory cells together with a population of plastic adherent umbilical cord derived mesenchymal stem cells. The therapy is described as reducing inflammation in the lungs of a subject suffering from lung inflammation, including lung fibrosis and ARDS, including COVID-19.
Preferred embodiments include T regulatory cells that enhance mesenchymal stem cell regenerative and anti-scarring activity via a GITR-dependent interaction. The document also discusses ex vivo and in vivo modulation concepts for achieving the inhibitory effect on lung inflammation.
The preferred embodiments specify the T regulatory cell phenotype and the mesenchymal stem cell population used in combination. T regulatory cells are described with marker features such as FoxP3, with optional features including TGF-beta, Helios, CD25, and IL-10, and mesenchymal stem cells are described as plastic adherent umbilical cord-derived cells, including embodiments described as JADI CELL™, with specified cellular marker profiles.
Claims Coverage
The partial content provides one independent claim directed to inhibiting lung inflammation, with dependent claims adding inventive refinements. Across the claims, the main inventive features focus on the identified subject with lung inflammation and reduction of lung inflammation using a Treg and plastic adherent umbilical cord-derived MSC combination, with optional narrowing to specific lung inflammation subtypes and defined marker and activation characteristics.
Subject identification and lung inflammation inhibition
A method for a subject suffering from lung inflammation includes administering a population of T regulatory cells in combination with a population of plastic adherent umbilical cord derived mesenchymal stem cells in an amount sufficient to reduce inflammation in the subject's lungs.
Lung fibrosis target
The method is directed to lung inflammation that is lung fibrosis.
GITR-expressing T regulatory cells
The method includes T regulatory cells that express GITR at a higher percentage than average T regulatory cells.
Marker-defined plastic adherent umbilical cord derived mesenchymal stem cells
The method uses a mesenchymal stem cell population that expresses specified cellular markers including CD7, CD11, CD90, CD105, CD133, and interleukin receptors, including interleukin 1 receptor, interleukin 3 receptor, interleukin 6 receptor, interleukin 13 receptor, interleukin 17 receptor, and interleukin 17F receptor.
Indolamine 2-3 deoxygenase activator selection
The indolamine 2-3 deoxygenase activator is selected from interferon alpha, interferon gamma, interferon beta, or interleukin 33.
COVID-19-caused ARDS target
The method is for ARDS that is caused by COVID-19.
Overall, the claims center on inhibiting lung inflammation by administering T regulatory cells together with plastic adherent umbilical cord-derived mesenchymal stem cells, with dependent claim refinements specifying lung fibrosis or COVID-19-caused ARDS, defining GITR expression levels on Tregs, defining MSC marker profiles, and specifying an indolamine 2-3 deoxygenase activator selection.
Stated Advantages
Reduces inflammation in the subject's lungs.
Enhances mesenchymal stem cell regenerative and anti-scarring activity via a GITR-dependent interaction.
Documented Applications
Inhibiting lung inflammation in subjects suffering from lung inflammation, including lung fibrosis.
Treatment of ARDS caused by COVID-19.
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