Methods and compositions for treating inflammatory conditions associated with infectious disease
Inventors
Pettine, Kenneth Allen • HICOK, Kevin • MOSELEY, Timothy Alexander
Assignees
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Publication Number
US-12570980-B2
Publication Date
2026-03-10
Expiration Date
Abstract
Disclosed herein are compositions comprising a mesenchymal stem cell (MSC) preparation and one or more biomolecules and the use of said compositions for the treatment or a microbial infection or the symptoms or secondary pathological conditions associated with said infection.
Core Innovation
The invention describes an acellular bone marrow mesenchymal stem cell (MSC) secretome composition for treating acute respiratory distress syndrome (ARDS). The secretome composition comprises stem cell factor 1 (SCF1), ferritin protein, TIMP1 (tissue inhibitor of metalloproteinases 1), and IGFBP-4 (insulin-like growth factor binding protein-4).
The described secretome concept is presented as an MSC-derived extracellular vesicle-based formulation combined with biomolecules, including specific proteins and microRNAs. The disclosed material includes extracellular vesicles associated with candidate proteins and microRNAs, including hsa-let-7 family members and selected hsa-miRNAs such as hsa-miR-21-5p, hsa-miR-24-3p, hsa-miR-27b-3p, and hsa-miR-222-3p.
The background problem addressed is severe lung dysfunction characterized by ARDS and related inflammatory and vascular pathologies, including cytokine storm and bradykinin storm, with downstream outcomes such as lung damage, impaired oxygen uptake, and airway epithelial cell injury. The described approach links administration of the MSC secretome composition with amelioration of these ARDS-associated effects.
Claims Coverage
The relevant independent claim is directed to a method for treating ARDS by administering a specific bone marrow MSC secretome composition with defined protein components, where treatment is defined by improving lung physiology and injury endpoints. Dependent claims further define additional biomolecules, extracellular vesicle characteristics, formulation forms, and preparation- and delivery-related constraints.
Msc secretome for ards treatment defined by lung function and injury endpoints
Administering to a subject in need thereof a bone marrow mesenchymal stem cell (MSC) secretome composition comprising SCF1, ferritin protein, TIMP1, and IGFBP-4, wherein the treating comprises ameliorating fluid leakage in the lungs, improving oxygen uptake in the lungs, ameliorating lung damage, and/or ameliorating airway epithelial cell injury.
Extracellular vesicle size range in the MSC secretome
The secretome composition comprises extracellular vesicles sized approximately 20 nm to 200 nm.
Extracellular vesicle concentration ranges for liquid versus lyophilized powder
The secretome composition includes extracellular vesicles at specified concentration ranges depending on whether the composition is a liquid or a lyophilized powder composition.
Parenteral administration of the MSC secretome treatment
Administering the treatment using parenteral administration.
Oxygen-level constraint for culturing MSCs to prepare the composition
Preparing the composition by culturing bone marrow mesenchymal stem cells (MSCs) under an oxygen level of 0.1% to 5%.
Specific microRNA subset included in the composition
The composition includes hsa-miR-21-5p, hsa-miR-24-3p, hsa-miR-222-3p, and hsa-miR-27b-3p.
Overall, the claim set centers on ARDS treatment using a bone marrow MSC secretome composition defined by SCF1, ferritin protein, TIMP1, and IGFBP-4, with treatment outcomes framed as reduced lung fluid leakage, improved oxygen uptake, and amelioration of lung damage and airway epithelial cell injury. Dependent coverage further specifies extracellular vesicle size and concentration ranges, formulation form, parenteral administration, MSC culturing oxygen level, and inclusion of particular microRNAs.
Stated Advantages
Ameliorates fluid leakage in the lungs.
Improves oxygen uptake in the lungs.
Ameliorates lung damage.
Ameliorates airway epithelial cell injury.
Documented Applications
Treating acute respiratory distress syndrome (ARDS) by administering a bone marrow MSC secretome composition.
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