Abstract: Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

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.

Abstract: This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis.

Abstract: Described herein are methods and compositions for use in expanding alveolar epithelial cells. The methods may include the use of three-dimensional substrates and improved techniques for expansion of the cells. The improved composition for culturing alveolar epithelial cells may include at least one or more of the following: a TGF-? pathway inhibitor; a Wnt pathway activator; a ROCK inhibitor; an epidermal growth factor (EGF); a keratinocyte growth factor (KGF); and a fetal bovine serum.

Abstract: Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

Abstract: A method for treating inflammatory diseases is provided. The method may include administering to a subject in need thereof a therapeutically effective amount of isolated extracellular vesicles or exosomes obtained from mesenchymal stem cells pre-conditioned with at least TNF-?. The isolated extracellular vesicles or exosomes may exhibit (a) enhanced expression of flotillin-1, (b) enhanced expression of CD73, or (c) enhanced expression of IDO. A method of isolating extracellular vesicles or exosomes capable of treating an inflammatory disease is also provided, wherein the method may include (a) culturing stem cells in a growth medium, (b) then culturing the stem cells in a starve medium supplemented with at least TNF-?, and (c) separating exosomes or extracellular vesicles from the culture. Cultures suitable for treatment are also provided.

Abstract: The current application is directed to a method for treating pulmonary arterial hypertension (PAH), comprising: providing isolated endothelial progenitor cells (EPCs); treating the EPCs with prostacyclin, wherein the treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic property; and administering a composition comprising the treated EPCs into a subject suffering from PAH.

Abstract: Disclosed here includes a method for purifying a biologic composition, comprising diafiltering the biologic composition into a composition comprising phosphate buffered saline (PBS) to obtain a purified composition. The method disclosed here can be particularly useful for removing one or more impurities from the biologic composition, such as bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane (Bis-tris).

Abstract: Methods and compositions relating to isolated mitochondria are disclosed. For example, cells, tissues, or organs can be treated with isolated mitochondria, such as porcine mitochondria, to improve mitochondrial function in the cell, tissue, or organ. The improvements to mitochondrial function include increased oxygen consumption and increased ATP synthesis. Such methods and compositions are useful for cell therapy; organ and tissue transplantation; organ and tissue engineering; and cold storage or shipment of harvested organs, tissues, and cells.

Abstract: An apparatus for exchanging small molecules with a fluid includes a small-molecule conduit for providing a first fluid having a first type of small molecule, a target fluid conduit for providing a target fluid having a second type of small molecule therein, and a carrier fluid conduit for providing a carrier fluid that is configured (i) to receive at least some of the first type of small molecule from the first fluid and transfer at least some of the first type of small molecule to the target fluid and (ii) to receive at least some of the second type of small molecule from the target fluid and transfer at least some of the second type of small molecule to the first fluid. The apparatus further includes an exchange module having an exchange chamber in fluid communication with the small-molecule conduit, the target fluid conduit and the carrier fluid conduit.

Abstract: The present disclosure provides regioselective methods for synthesizing intermediates useful in making prostacyclin derivatives, such as treprostinil.

Abstract: The current application is directed to a method for treating pulmonary arterial hypertension (PAH), comprising: providing isolated endothelial progenitor cells (EPCs); treating the EPCs with prostacyclin, wherein the treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic property; and administering a composition comprising the treated EPCs into a subject suffering from PAH.

Abstract: An automated bioreactor system for decellularizing an organ includes a main chamber for containing the organ. The system further includes a reagent chamber containing a liquid phase reagent. A reagent conduit delivers the liquid phase reagent to the main chamber, and a perfusion conduit delivers the reagent from the reagent outlet in the main chamber into the organ. A perfusion pump drives the flow of the reagent. A perfusion pressure sensor detects a pressure of the flowing reagent. A control system controls the perfusion pump to drive the flow of the reagent based on a received input representative of a desired pressure and a received input of the detected pressure. The control system may automatically perform all of the steps of a decellularization protocol based on sensor input. An automated waste decontamination system may also be provided.

Abstract: An adjustable aerosol delivery device includes an active liquid container, a carrier liquid container, a piezo disc mounted with a flexible gasket relative to the carrier liquid container, an oscillator configured to generate an ultrasonic wave that causes the piezo disc to oscillate and transmit the oscillations through the carrier liquid to the active liquid to cause at least a portion of the active liquid to become an aerosol, a bushing fixed relative to the carrier liquid container via a fixing portion that conforms to and mates with an entire perimeter of a fixing section of the bushing, and a fastener extending through the piezo disc housing and into the bushing. The fastener is configured to be loosened or tightened to manipulate a compression of the gasket to adjust a particle size of the aerosol. A pull force of the bushing is greater than a counter force of the gasket.

Abstract: A dosage inhaler includes an active liquid container, which contains a liquid having an active ingredient dissolved therein, and an atomizer by which the liquid is transformed into an aerosol and can be introduced into an aerosol dome, in which there is a baffle plate and to which an inlet tube and an outlet tube are attached, and an electronic control. The atomizer can be intermittently operated by a user and the user command readout is visible to the user. The generation of the amount of aerosol inside, and below, the aerosol dome is able to be separated in time from its eventual inhalation by the user.

Abstract: An adjustable aerosol delivery device includes an active liquid container, a carrier liquid container, a piezo disc mounted with a flexible gasket relative to the carrier liquid container, an oscillator configured to generate an ultrasonic wave that causes the piezo disc to oscillate and transmit the oscillations through the carrier liquid to the active liquid to cause at least a portion of the active liquid to become an aerosol, a bushing fixed relative to the carrier liquid container via a fixing portion that conforms to and mates with an entire perimeter of a fixing section of the bushing, and a fastener extending through the piezo disc housing and into the bushing. The fastener is configured to be loosened or tightened to manipulate a compression of the gasket to adjust a particle size of the aerosol. A pull force of the bushing is greater than a counter force of the gasket.

Abstract: The present disclosure provides regioselective methods for synthesizing intermediates useful in making prostacyclin derivatives, such as treprostinil.

Abstract: An automated bioreactor system for decellularizing an organ includes a main chamber for containing the organ. The system further includes a reagent chamber containing a liquid phase reagent. A reagent conduit delivers the liquid phase reagent to the main chamber, and a perfusion conduit delivers the reagent from the reagent outlet in the main chamber into the organ. A perfusion pump drives the flow of the reagent. A perfusion pressure sensor detects a pressure of the flowing reagent. A control system controls the perfusion pump to drive the flow of the reagent based on a received input representative of a desired pressure and a received input of the detected pressure. The control system may automatically perform all of the steps of a decellularization protocol based on sensor input. An automated waste decontamination system may also be provided.

Abstract: The present invention describes novel methods for using Treprostinil or its derivative, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of ischemic lesions, such as digital ulcers, in subjects with scleroderma (including systemic sclerosis), Buerger's disease, Raynaud's disease, Raynaud's phenomenon and/or other conditions that cause such lesions. The invention also relates to kits for treatment and/or prevention of ischemic lesions, comprising an effective amount of Treprostinil or its derivative, or a pharmaceutically acceptable salt thereof.

Abstract: Treprostinil can be administered using a metered dose inhaler. Such administration provides a greater degree of autonomy to patients. Also disclosed are kits that include a metered dose inhaler containing a pharmaceutical formulation containing treprostinil.