Use of Toll-Like Receptor 4 Agonists to Treat Inflammation and Tissue Injury
AssigneeWisconsin Alumni Research Foundation
InventorsPeiman HEMATTI, John KINK, Christian CAPITINI, Matthew FORSBERG, Nicholas HESS, Zachary ROSENKRANS, Reinier HERNANDEZ
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Abstract
The disclosure relates to populations of educated macrophages and monocytes generated ex vivo or in vivo, and methods of making and using the same using lipid A aminoalkylglucosaminide phosphate molecules, such as CRX molecules or extracellular vesicles (EVs) from mesenchymal stromal cells (MSC) stimulated with CRX molecules. Also described are EVs and methods for making and using the same from MSCs exposed to CRX.
Claims41
A method for generating an educated CD14+ cell, the method comprising:
- co-culturing a CD14+ cell in vitro (i) with an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a synthetic lipid A aminoalkyl glucosaminide phosphate (AGP) molecule or (ii) with a synthetic lipid A AGP molecule, until the CD14+ cell acquires an anti-inflammatory macrophage or monocyte phenotype.
A method for generating an extracellular vesicle, the method comprising:
- co-culturing a mesenchymal stromal cell with a CRX molecule for at least 2 hours, wherein an extracellular vesicle is formed, and
- optionally isolating extracellular vesicles from the co-culture, wherein an extracellular vesicle is formed.
A method for treating acute radiation syndrome in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of
- (i) a CD14+ cell that has been co-cultured with an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EEM or CRX-EEMos;
- (ii) an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EVs;
- or
- (iii) a CD14+ cell treated with a CRX molecule (CRX-EM or CRX-EMos),
- wherein the acute radiation syndrome is effectively treated in the subject.
A method for treating or preventing graft-versus-host-disease in a subject undergoing a transplant, the method comprising:
- administering to the subject a therapeutically effective amount
- (i) a CD14+ cell that has been co-cultured with an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EEM or CRX-EEMos;
- (ii) an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EVs;
- or
- (iii) a CD14+ cell treated with a CRX molecule (CRX-EM or CRX-EMos), wherein the graft-versus-host-disease is suppressed in the subject.
A method for treating or preventing acute kidney injury in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of
- (i) a CD14+ cell that has been co-cultured with an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EEM or CRX-EEMos;
- (ii) an extracellular vesicle isolated from a mesenchymal stromal cell previously exposed to a CRX molecule, generating CRX-EVs;
- or
- (iii) a CD14+ cell treated with a CRX molecule (CRX-EM or CRX-EMos),
- wherein the acute kidney injury is effectively treated in the subject.
Dependencies are inferred from the claim text.