# US 12,467,035 B2 · Method of differentiating mesenchymal stem cells into cardiomyocytes

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- Number: US 12,467,035 B2
- Document ID: US12467035B2
- Status: Granted
- Kind: B2
- Application number: 15/854,017
- Filed: 2017-12-26
- Published: 2018-07-19
- Granted: 2025-11-11
- Earliest claimed: 2016-12-27
- Assignees: Chonnam National University Hospital
- Applicants: Chonnam National University Hospital
- Inventors: Youngkeun Ahn; Yong Sook Kim; Hye Jin Kang; Dong Im Cho
- Web page: https://patentgrep.com/patent/US12467035B2

## CPC

- C12N 5/0657: {Cardiomyocytes; Heart cells}
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- C12N 2500/30: Organic components
- C12N 2500/34: Sugars
- C12N 2501/065: Modulators of histone acetylation
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2506/1353: from bone marrow mesenchymal stem cells (BM-MSC)
- C12N 2510/00: Genetically modified cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to a method of differentiating mesenchymal stem cells into cardiomyocytes. When the method of the present invention is used, cardiomyocytes may be obtained from mesenchymal stem cells with high efficiency. Therefore, the method of the present invention may be effectively used for treatment of heart diseases, such as heart failure, which require myocardial regeneration for treatment.

## Claims

### Claim 1

A method of inducing differentiation of mesenchymal stem cells into cardiomyocytes, the method comprising treating adult mesenchymal stem cells by culturing the adult mesenchymal stem cells in a medium consisting of glucose-free basal culture medium and apicidin or in a medium consisting of glucose-free basal culture medium, apicidin and lactic acid, wherein apicidin induces differentiation of mesenchymal stem cells into cardiomyocytes,
then washing the cultured cells to produce cardiomyocytes, wherein the culturing is performed for 4 to 27 hours and wherein the expression of cardiomyocyte-specific markers is increased in the cardiomyocytes compared to the adult mesenchymal stem cells.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the adult mesenchymal stem cells are obtained from bone marrow, tissue, embryos, cord blood, blood or bodily fluids.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the cardiomyocyte-specific markers are selected from the group consisting of GATA4, Nkx2.5, cardiac troponin I (cTnI), cardiac troponin T (cTnT), a myosin light chain (MLC), a myosin heavy chain (MHC), and connexin 43 (Cx43).

### Claim 4 (depends on 1)

The method according to claim 1, wherein the concentration of apicidin is 3 μM and the concentration of lactic acid is 12 mM.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the culturing is performed for at least 20 hours.