# US 9,518,251 B2 · Method for enhancing therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases

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- Number: US 9,518,251 B2
- Document ID: US9518251B2
- Status: Granted
- Kind: B2
- Application number: 15/074,490
- Filed: 2016-03-18
- Published: 2016-07-21
- Granted: 2016-12-13
- Earliest claimed: 2014-09-17
- Assignees: Gwo Xi Stem Cell Applied Technology Co., Ltd.
- Applicants: Gwo Xi Stem Cell Applied Technology Co., Ltd.
- Inventors: Shinn-Zong Lin; Horng-Jyh Harn; Ru-Huei Fu; Shih-Ping Liu; Po-Cheng Lin; Ming-Hsi Chuang
- Web page: https://patentgrep.com/patent/US9518251B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 31/365: Lactones
- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 37/02: Immunomodulators
- C12N 5/0667: {Adipose-derived stem cells [ADSC]; Adipose stromal stem cells}
- C12N 2501/40: Regulators of development
- C12N 2501/999: Small molecules not provided for elsewhere
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A method for enhancing the therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases is provided. The method comprises pre-treating the stem cells with ligustilide to increase the expression of differentiation-promoting genes in the stem cells, increase the expression of homing-promoting genes in the stem cells, and/or decrease the expression of inflammatory genes in the stem cells, wherein the treatment is conducted in a culture medium of the stem cell.

## Claims

### Claim 1

A method for enhancing the therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases, comprising:
a) pre-treating the stem cells by culturing the stem cells in a culture medium comprising 0.1 μg/ml to 20 μg/ml of ligustilide to increase the expression of differentiation-promoting genes in the stem cells, increase the expression of homing-promoting genes in the stem cells, and/or decrease the expression of inflammatory genes in the stem cells, wherein the culture medium does not comprise insulin; and
b) administering an effective amount of stem cells pre-treated in step a) to a subject suffering from autoimmune diseases, cardiovascular diseases and/or hematological diseases.

### Claim 2 (depends on 1)

The method of claim 1, wherein the stem cell is an embryonic stem cell, an adult stem cell, or an induced pluripotent stem cell.

### Claim 3 (depends on 2)

The method of claim 2, wherein the stem cells are adipose-derived stem cells.

### Claim 4 (depends on 1)

The method of claim 1, wherein the culture medium comprises 0.1 μg/ml to 10 μg/ml of ligustilide.

### Claim 5 (depends on 4)

The method of claim 4, wherein the culture medium comprises 0.5 μg/ml to 5 μg/ml of ligustilide.

### Claim 6 (depends on 1)

The method of claim 1, wherein the method is used for enhancing the therapeutic effect of stem cells on cardiovascular diseases, comprising:
a) pre-treating the stem cells by culturing the stem cells in a culture medium comprising 0.1 μg/ml to 20 μg/ml of ligustilide to increase the expression of differentiation-promoting genes in the stem cells, increase the expression of homing-promoting genes in the stem cells, and/or decrease the expression of inflammatory genes in the stem cells, and the culture medium does not comprise insulin; and
b) administering an effective amount of stem cells pre-treated in step a) to a subject suffering from cardiovascular diseases.

### Claim 7 (depends on 6)

The method of claim 6, wherein the stem cell is an embryonic stem cell, an adult stem cell, or an induced pluripotent stem cell.

### Claim 8 (depends on 7)

The method of claim 7, wherein the stem cells are adipose-derived stem cells.

### Claim 9 (depends on 6)

The method of claim 6, wherein the cardiovascular disease is stroke.

### Claim 10 (depends on 6)

The method of claim 6, wherein the culture medium comprises 0.1 μg/ml to 10 μg/ml of ligustilide.

### Claim 11 (depends on 10)

The method of claim 10, wherein the culture medium comprises 0.5 μg/ml to 5 μg/ml of ligustilide.

### Claim 12 (depends on 1)

The method of claim 1, wherein the method is used for enhancing the therapeutic effect of stem cells on hematological diseases, comprising:
a) pre-treating the stem cells by culturing the stem cells in a culture medium comprising 0.1 μg/ml to 20 μg/ml of ligustilide to increase the expression of differentiation-promoting genes in the stem cells, increase the expression of homing-promoting genes in the stem cells, and/or decrease the expression of inflammatory genes in the stem cells, and the culture medium does not comprise insulin; and
b) administering an effective amount of stem cells pre-treated in step a) to a subject suffering from hematological diseases.

### Claim 13 (depends on 12)

The method of claim 12, wherein the stem cell is an embryonic stem cell, an adult stem cell, or an induced pluripotent stem cell.

### Claim 14 (depends on 13)

The method of claim 13, wherein the stem cells are adipose-derived stem cells.

### Claim 15 (depends on 12)

The method of claim 12, wherein the culture medium comprises 0.1 μg/ml to 10 μg/ml of ligustilide.

### Claim 16 (depends on 15)

The method of claim 15 wherein the culture medium comprises 0.5 μg/ml to 5 μg/ml of ligustilide.