Treatment of pulmonary arterial hypertension with mesenchymal stem cells

Patent metadata

Field	Value
Publication number	US-11666602-B2
Application number	US-201816124532-A
Country	US
Kind code	B2
Filing date	Sep 7, 2018
Priority date	Aug 1, 2012
Publication date	Jun 6, 2023
Grant date	Jun 6, 2023

Abstract

The application is directed to a method for treating or preventing vasculopathy comprising administrating to a subject in need thereof a pharmaceutical composition comprising mesenchymal precursor cells (MPCs) and a prostacyclin. Also provided a method 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

What is claimed is:

1. A method for treating pulmonary hypertension, comprising administrating to a human subject in need thereof a pharmaceutical composition comprising mesenchymal precursor cells (MPCs) pre-treated ex vivo with treprostinil or a pharmaceutically acceptable salt thereof during expansion of the MPCs.

2. The method of claim 1 , wherein the MPCs are obtained from bone marrow of the subject.

3. The method of claim 1 , wherein the pharmaceutical composition further comprises at least one pharmaceutically-acceptable carrier.

4. The method of claim 1 , wherein the pharmaceutical composition further comprises at least one therapeutic agent.

5. The method of claim 1 , further comprising reducing thrombosis in pulmonary arteries, reducing inflammation in pulmonary arteries, reducing the proliferation of intimal smooth muscle in pulmonary arteries, and/or reducing the formation of plexiform lesions in pulmonary arteries.

6. The method of claim 1 , further comprising increasing the amount of nitric oxide in pulmonary arteries, increasing the amount of PGI 2 in pulmonary arteries, and/or reducing the level of Endothelin-1 in pulmonary arteries.

7. The method of claim 1 , further comprising reducing the amount of growth factors in pulmonary arteries, and/or promoting proper endothelial morphology in pulmonary arteries.

8. The method of claim 1 , wherein at least some of the MPCs are genetically modified.

9. The method of claim 1 , wherein the composition is co-administered with endothelial progenitor cells.

10. The method of claim 1 , wherein the composition is co-administered to the subject with at least one of a phosphodiesterase-5 (PDE-5) inhibitor, an endothelin receptor antagonist (ETRA), a tyrosine kinase inhibitors, and a soluble guanylate cyclase stimulator.

11. A method for treating pulmonary hypertension in a subject in need thereof, comprising administering to the subject treprostinil or a pharmaceutically acceptable salt thereof and a composition comprising 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, wherein the MSC was pre-treated with ex vivo with treprostinil or a pharmaceutically acceptable salt thereof during expansion of the MSC.

12. The method of claim 11 , wherein treprostinil or the pharmaceutically acceptable salt thereof and the composition are administered concurrently.

13. The method of claim 11 , wherein treprostinil or the pharmaceutically acceptable salt thereof and the composition are administered separately.

14. The method of claim 11 , 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.

15. The method of claim 11 , further comprising administering to the subject an endothelial progenitor cell (EPC).

16. The method of claim 15 , wherein the EPC is obtained from the subject.

17. The method of claim 15 , 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).

18. The method of claim 17 , wherein the nucleic acid encodes the protein.

19. The method of claim 11 , wherein the MSC is a mesenchymal precursor cell (MPC).

20. The method of claim 11 , wherein the MSC is obtained from bone marrow.

Assignees

• United Therapeutics Corp

Inventors

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

Classifications

• A61K35/28 Primary

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C12N2501/02

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C12N5/0692

  Stem cells; Progenitor cells; Precursor cells · CPC title