Novel method to alter the proteome of a diseased heart by injection of ecm particles produced from decellularized 3d microtissues of human mesenchymal stem cells

Patent metadata

Field	Value
Publication number	US-2025242080-A1
Application number	US-202519067759-A
Country	US
Kind code	A1
Filing date	Feb 28, 2025
Priority date	Dec 23, 2020
Publication date	Jul 31, 2025
Grant date	—

Abstract

This disclosure describes a method for altering the proteome of a diseased heart, organ or tissue by contacting it with extracellular matrix (ECM) particles derived from decellularized 3D microtissues. In an example, the process involves restoring the normal ratio of collagen levels, modulating immune responses, improving mitochondrial function, and/or mitigating the effects of TGF-Beta, a growth factor associated with fibrosis. The ECM particles can be produced from human mesenchymal stem cells and retain bioactive components and structural properties of native tissue. Additionally, the disclosure outlines a composition for treating a diseased organ using these ECM particles, which are treated to enhance crosslinking, stability, injectability, and compatibility with patients.

First claim

We claim:

1 . A method of altering the proteome of a diseased heart, comprising:
contacting the diseased heart with extra-cellular matrix (ECM) particles produced from decellularized 3D microtissues, wherein the contacting alters the proteome of the diseased heart.

2 . The method of claim 1 , wherein the contacting restores a normal ratio of levels of different collagens in the heart.

3 . The method of claim 1 , wherein the contacting alters an immune response in the heart.

4 . The method of claim 1 , wherein the contacting alters metabolism in the heart.

5 . The method of claim 1 , wherein the contacting mitigates effects of TGF-Beta in the heart, wherein TGF-Beta is a growth factor associated with fibrosis.

6 . The method of claim 1 , wherein the 3D microtissues are derived from human mesenchymal stem cells.

7 . A method of treating a diseased heart, comprising:
administering to the diseased heart extra-cellular matrix (ECM) particles produced from decellularized 3D microtissues, wherein the administering treats the diseased heart by altering the proteome of the diseased heart.

8 . The method of claim 7 , wherein the administering restores a normal ratio of levels of different collagens in the heart.

9 . The method of claim 7 , wherein the administering alters an immune response in the heart.

10 . The method of claim 7 , wherein the administering alters metabolism in the heart.

11 . The method of claim 7 , wherein the administering mitigates effects of TGF-Beta in the heart, wherein TGF-Beta is a growth factor associated with fibrosis.

12 . The method of claim 7 , wherein the 3D microtissues are derived from human mesenchymal stem cells.

13 . Extra-cellular matrix (ECM) particles for altering the proteome of a diseased heart, wherein the ECM particles are produced from decellularized 3D microtissues and treated to improve one or more of crosslinking, stability, injectability, or compatibility with a patient.

14 . The ECM particles of claim 13 , wherein the ECM particles, when contacted with the diseased heart, restore a normal ratio of levels of different collagens in the heart.

15 . The ECM particles of claim 13 , wherein the ECM particles, when contacted with the diseased heart, alter an immune response in the heart.

16 . The ECM particles of claim 13 , wherein the ECM particles, when contacted with the diseased heart, alter metabolism in the heart.

17 . The ECM particles of claim 13 , wherein the ECM particles, when contacted with the diseased heart, mitigate effects of TGF-Beta in the heart, wherein TGF-Beta is a growth factor associated with fibrosis.

18 . The ECM particles of claim 13 , wherein the 3D microtissues are derived from human mesenchymal stem cells.

19 . A composition for treating a diseased heart, comprising:
extra-cellular matrix (ECM) particles produced from decellularized 3D microtissues and treated to improve one or more of crosslinking, stability, injectability, or compatibility with a patient; wherein the composition, when administered to the diseased heart, treats the diseased heart by altering the proteome of the diseased heart.

20 . The composition of claim 19 , wherein the 3D microtissues are derived from human mesenchymal stem cells.

Assignees

• Univ Brown
• Xm Therapeutics Inc

Inventors

• Morgan Jeffrey R
• Ahmann Frank
• Petersen Max Johan

Classifications

• A61L2430/20

  for reconstruction of the heart, e.g. heart valves · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L27/3687

  characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents · CPC title

• A61L27/3641

  characterised by the site of application in the body (materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60) · CPC title