Treatment of pulmonary arterial hypertension with prostacyclin-treated endothelial progenitor cells

Inventors

Jeffs, RogerPetersen, ThomasIlagan, Roger M.Wade, Michael

Assignees

United Therapeutics Corp

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Publication Number

US-12310992-B2

Patent

Publication Date

2025-05-27

Expiration Date


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.

Core Innovation

The invention relates to treating pulmonary arterial hypertension by administering isolated endothelial progenitor cells that are treated with prostacyclin ex vivo. The treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic activity. The prostacyclin is provided as epoprostenol, treprostinil, ilprost, and PGI2 receptor agonists.

The EPCs are treated in vitro or ex vivo with a prostacyclin during expansion of the EPCs, and the treated EPC composition is then administered to a human subject suffering from pulmonary hypertension. The disclosure includes embodiments involving EPC growth and promotion and prostacyclin administration in association with EPC preparation and use.

The disclosure also includes embodiments involving EPC co-administration with growth factors and mesenchymal stem cell products, including MSC-conditioned medium and exosome-type vesicles. It further describes EPC phenotyping markers such as CD45, VEGFR-2, and Tie-2, with an optionally described marker CD14, and genetic modification examples including eNOS, HMOX1, and PTGIS.

Claims Coverage

The independent claim covers a method of treating pulmonary arterial hypertension using treated EPCs, with two main inventive features.

Prostacyclin-treated EPC expansion for hyperproliferative angiogenic phenotype

Treating isolated EPCs in vitro or ex vivo with a prostacyclin during expansion of the EPCs, wherein the treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic activity.

Administering treated EPC composition to a human subject with pulmonary hypertension

Administering a composition comprising the treated EPCs to a human subject suffering from pulmonary hypertension.

Across the independent claim, EPCs are expanded after prostacyclin treatment to obtain a hyperproliferative phenotype with enhanced angiogenic activity, and the treated EPC composition is administered to a human subject suffering from pulmonary hypertension.

Stated Advantages

Produces treated EPCs with a hyperproliferative phenotype with enhanced angiogenic activity.

Provides a method for treating pulmonary arterial hypertension by administering the treated EPCs to a human subject suffering from pulmonary hypertension.

Documented Applications

Treating pulmonary arterial hypertension in a human subject by administering a composition comprising prostacyclin-treated, expanded EPCs with enhanced angiogenic activity.

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