# US 2014/0193909 A1 · Direct Differentiation of Cardiomyocytes From Embryonic Stem Cells

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- Number: US 2014/0193909 A1
- Document ID: US20140193909A1
- Status: Published application
- Kind: A1
- Application number: 13/651,151
- Filed: 2012-10-12
- Published: 2014-07-10
- Earliest claimed: 2005-12-22
- Assignees: ES Cell International PTE Ltd.
- Applicants: ES Cell International Pte Ltd
- Inventors: Bruce Paul Davidson; Ralph Eberhard Graichen; Robert Zweigerdt; Xiuqin Xu; Christine Lindsay Mummery; William Sun
- Web page: https://patentgrep.com/patent/US20140193909A1

## CPC

- C12N 5/0657: {Cardiomyocytes; Heart cells}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5061: {Muscle cells}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- C12N 5/0043: {Medium free of human- or animal-derived components}
- C12N 2500/25: Insulin-transferrin; Insulin-transferrin-selenium
- C12N 2500/99: Serum-free medium
- C12N 2501/02: Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes
- C12N 2501/105: Insulin-like growth factors [IGF]
- C12N 2501/115: Basic fibroblast growth factor (bFGF, FGF-2)
- C12N 2501/125: Stem cell factor [SCF], c-kit ligand [KL]
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/33: Insulin
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2502/13: connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N 2502/30: tumour cells
- C12N 2506/02: from embryonic cells
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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 the induction of differentiation in human embryonic stem (hES) cells to cardiomyocytes and factors such as prostaglandin I2 (PGI2), Fgf 9, Bmp6, Bmp4, Scf, Igf2, and insulin that influence the process of differentiation to cardiomyocytes. Media that is appropriate for the induction of differentiation of cardiomyocytes from hES cells is also provided wherein the media contains these factors. Genes that are upregulated in the process of cardiomyocyte differentiation are also provided.

## Claims

### Claim at position 1

-34. (canceled)

### Claim 35

A cell culture media comprising a prostaglandin or an analog or functional equivalent thereof and a cardiac progenitor cell.

### Claim 36 (depends on 35)

The cell culture media of claim 35, wherein the cardiac progenitor cell beats.

### Claim 37 (depends on 35)

The cell culture media of claim 35, wherein the media is serum free.

### Claim 38 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises transferrin.

### Claim 39 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises selenium.

### Claim 40 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises BMP4.

### Claim 41 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises BMP6.

### Claim 42 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises FGF9.

### Claim 43 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises SCF.

### Claim 44 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises IGF2.

### Claim 45 (depends on 35)

The cell culture media of claim 35, wherein the media further comprises a p38 MAP kinase inhibitor.

### Claim 46 (depends on 45)

The cell culture media of claim 45, wherein the p38 MAP kinase inhibitor is SB203580.

### Claim 47

A cell culture media free of insulin and comprising PGI2.

### Claim 48 (depends on 47)

The cell culture media of claim 47, wherein the media is serum free.

### Claim 49 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises transferrin.

### Claim 50 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises selenium.

### Claim 51 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises BMP4.

### Claim 52 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises BMP6.

### Claim 53 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises FGF9.

### Claim 54 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises SCF.

### Claim 55 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises IGF2.

### Claim 56 (depends on 47)

The cell culture media of claim 47, wherein the media further comprises a p38 MAP kinase inhibitor.

### Claim 57 (depends on 56)

The cell culture media of claim 56, wherein the p38 MAP kinase inhibitor is SB203580.
