Treatment of vasculopathy with prostacyclin and mesenchymal stem cells

Patent metadata

Field	Value
Publication number	US-12274684-B2
Application number	US-202318535865-A
Country	US
Kind code	B2
Filing date	Dec 11, 2023
Priority date	Jan 9, 2013
Publication date	Apr 15, 2025
Grant date	Apr 15, 2025

Abstract

Provided are methods for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a mesenchymal stem cell (MSC) or a MSC-conditioned culture medium or administering to the subject a MSC or a MSC-conditioned culture medium that has treated with prostacyclin. Pharmaceutical compositions suitable for such treatments are also provided.

First claim

The invention claimed is:

1. A method of preparing a pharmaceutical product a mesenchymal stem cell (MSC) or a part of a culture medium that has been in contact with the MSC and contains one or more components of the MSC, comprising contacting a culture comprising an MSC with a prostacyclin and thereafter isolating the MSC or a part of a culture medium that has been in contact with the MSC and contains one or more components of the MSC.

2. The method of claim 1 , wherein the component(s) of the MSC is selected from the group consisting of an exosome, a microvesicle, a microRNA, a messenger RNA, a non-coding RNA, a mitochondria, a growth factor, and combinations thereof.

3. The method of claim 1 , wherein the pharmaceutical product further comprises an endothelial progenitor cell (EPC).

4. The method of claim 3 , wherein the EPC is obtained from a subject who is to be treated with the pharmaceutical product.

5. The method of claim 4 , wherein the EPC is transformed with a nucleic acid that increases the expression of biological activity of a protein selected from the group consisting of endothelial nitric oxide synthase (eNOS), heme oxygenase (HMOX1) and prostacyclin synthase (PTGIS).

6. The method of claim 5 , wherein the nucleic acid encodes the protein.

7. The method of claim 1 , wherein the prostacyclin is selected from the group consisting of epoprostenol, treprostinil, beraprost, ilprost, a PGI 2 receptor agonist, and pharmaceutically acceptable salts thereof.

8. The method of claim 7 , wherein the prostacyclin is treprostinil or a pharmaceutically acceptable salt or ester thereof.

9. The method of claim 1 , wherein the MSC is a mesenchymal precursor cell (MPC).

10. The method of claim 1 , wherein the MSC is obtained from bone marrow.

11. The method of claim 1 , wherein contacting with the prostacyclin comprises adding the prostacyclin to the MSC culture at a concentration from about 200 μg/mL to about 300 μg/mL.

12. The method of claim 1 , wherein the contacting with the prostacyclin occurs for at least 24 hours.

13. The method of claim 11 , wherein the contacting with the prostacyclin occurs for at least 24 hours.

14. The method of claim 13 , wherein the prostacyclin is treprostinil.

Assignees

• United Therapeutics Corp

Inventors

• Jeffs Roger
• Petersen Thomas
• Ilagan Roger M
• Wade Michael

Classifications

• A61K31/5585 Primary

  having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin · CPC title

• A61K31/557 Primary

  Eicosanoids, e.g. leukotrienes {or prostaglandins} · CPC title

• A61K35/28

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• C12N2501/02

  Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes · CPC title

• C12N2501/00

  Active agents used in cell culture processes, e.g. differentation · CPC title