Extracellular vesicles with enhanced potency
AssigneeUnited Therapeutics Corporation
InventorsSarah HOGAN, Roger Marquez ILAGAN, Maria Pia RODRIGUEZ, Carolina MEDRANO, John CHEADLE
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Abstract
Provided are methods for isolating potent extracellular vesicle or exosome populations from mesenchymal stromal cells, and the use of the isolated extracellular vesicles or exosomes in treating vasculopathy, including pulmonary hypertension, bronchopulmonary dysplasia, and disease and conditions associated with mitochondrial dysfunction.
Claims55
A method of treating pulmonary hypertension, comprising administering to a subject in need thereof isolated extracellular vesicles or exosomes obtained from mesenchymal stromal cells, wherein the isolated extracellular vesicles or exosomes comprise extracellular vesicles or exosomes having increased expression of one or more expression products selected from the group consisting of (a) genes in the glycolysis pathway, (b) genes in the TCA cycle, and (c) genes in the electron transport chain as compared to the average amount of the expression products in all extracellular vesicles or exosomes obtained from the mesenchymal stromal cells.
A method of treating a disease or condition associated with mitochondrial dysfunction, comprising administering to a subject in need thereof isolated extracellular vesicles or exosomes obtained from mesenchymal stromal cells, wherein the isolated extracellular vesicles or exosomes comprise extracellular vesicles or exosomes having increased expression of one or more expression products selected from the group consisting of (a) genes in the glycolysis pathway, (b) genes in the TCA cycle, and (c) genes in the electron transport chain as compared to the average amount of the expression products in all extracellular vesicles or exosomes obtained from the mesenchymal stromal cells.
The method of claim 13, wherein the isolated extracellular vesicles or exosomes a PK activity of at least 0.15 nmol/min/mL.
A method of isolating extracellular vesicles or exosomes capable of treating or preventing pulmonary hypertension, comprising the following steps:
- a. providing a culture media of mesenchymal stromal cells comprising extracellular vesicles or exosomes;
- b. separating at least a portion of the extracellular vesicles or exosomes from the other components of the culture media;
- c. isolating a extracellular vesicle or exosome population from other extracellular vesicle or exosome populations, wherein the population has increased expression of one or more expression products selected from the group consisting of (a) genes in the glycolysis pathway, (b) genes in the TCA cycle, and (c) genes in the electron transport chain as compared to the average amount of the expression products in all extracellular vesicles or exosomes obtained from the mesenchymal stromal cells.
A method of isolating extracellular vesicles or exosomes capable of treating or preventing pulmonary hypertension, comprising the following steps:
- a. providing a culture media of mesenchymal stromal cells comprising extracellular vesicles or exosomes;
- b. separating at least a portion of the extracellular vesicles or exosomes from the other components of the culture media;
- c. separating different populations of extracellular vesicles or exosomes based on molecular size;
- d. treating hypoxia-exposed mice with the different populations of extracellular vesicles or exosomes;
- e. measuring Right Ventricular Systolic Pressure (RVSP) of normoxia mice, hypoxia-exposed mice and hypoxia exposed mice treated with the extracellular vesicles or exosomes;
- f. identifying a potent population of extracellular vesicles or exosomes based on the RVSP.
A method of isolating extracellular vesicles or exosomes capable of treating or preventing bronchopulmonary dysplasia, comprising the following steps:
- a. providing a culture media of mesenchymal stromal cells comprising extracellular vesicles or exosomes;
- b. separating at least a portion of the extracellular vesicles or exosomes from the other components of the culture media;
- c. separating different populations of extracellular vesicles or exosomes based on molecular size;
- d. treating hypoxia-exposed mice with the different populations of extracellular vesicles or exosomes;
- e. measuring Right Ventricular Systolic Pressure (RVSP) of normoxia mice, hypoxia-exposed mice and hypoxia exposed mice treated with the extracellular vesicles or exosomes;
- f. identifying a potent population of extracellular vesicles or exosomes based on the RVSP.
Dependencies are inferred from the claim text.