# US 9,517,248 B2 · Adherent cells from adipose or placenta tissues and use thereof in therapy

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- Number: US 9,517,248 B2
- Document ID: US9517248B2
- Status: Granted
- Kind: B2
- Application number: 14/180,039
- Filed: 2014-02-13
- Published: 2014-08-28
- Granted: 2016-12-13
- Earliest claimed: 2007-09-19
- Assignees: Pluristem Ltd.
- Applicants: Pluristem Ltd.
- Inventors: Moran Meiron; Amir Toren; Rachel Ofir; Zami Aberman; Nirit Drori-Carmi
- Web page: https://patentgrep.com/patent/US9517248B2

## CPC

- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/35: Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39)
- A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method of treating ischemia in a subject in need thereof is disclosed. The method comprising administering to the subject a therapeutically effective amount of adherent cells of a tissue selected from the group consisting of a placenta and an adipose tissue, thereby treating the ischemia in the subject. A method of treating a medical condition requiring connective tissue regeneration and/or repair is also disclosed.

## Claims

### Claim 1

A method of treating a wound in a subject in need thereof, comprising systemically administering to the subject a therapeutically effective amount of undifferentiated placenta-derived adherent stromal cells in a liquid suspension, wherein the adherent stromal cells do not express CD34, thereby treating the wound.

### Claim 2 (depends on 1)

The method of claim 1, wherein at least 10% of said cells are at a proliferative phase.

### Claim 3 (depends on 1)

The method of claim 1, wherein the wound is a wound to the skin.

### Claim 4 (depends on 1)

The method of claim 1, wherein said cells have been propagated in three-dimensional (3D) culturing conditions.

### Claim 5 (depends on 4)

The method of claim 4, wherein said three-dimensional (3D) culturing conditions comprise a 3D bioreactor.

### Claim 6 (depends on 4)

The method of claim 4, wherein said three-dimensional (3D) culturing conditions are effected under perfusion.

### Claim 7 (depends on 4)

The method of claim 4, wherein said three-dimensional (3D) culturing conditions comprise an adherent material selected from the group consisting of a polystyrene, a polyester, and a polypropylene.

### Claim 8 (depends on 1)

The method of claim 1, wherein said cells have been cultured for at least 3 days.

### Claim 9 (depends on 1)

The method of claim 1, wherein said cells have been cultured until at least 10% of said cells are proliferating.

### Claim 10 (depends on 4)

The method of claim 4, wherein said cells express a marker selected from the group consisting of CD73, CD90, CD29 and CD105.

### Claim 11 (depends on 4)

The method of claim 4, wherein said cells do not express a marker selected from the group consisting of CD3, CD4, CD45, CD80, HLA-DR, CD11b, CD14, CD19 and CD79.

### Claim 12 (depends on 6)

The method of claim 6, wherein said perfusion rate is adjusted in order to maintain a constant glucose concentration in the culture medium.

### Claim 13 (depends on 12)

The method of claim 12, wherein said constant glucose concentration is about 550 mg/L.

### Claim 14 (depends on 1)

The method of claim 1, wherein said cells have been propagated in two-dimensional (2D) culturing conditions.

### Claim 15 (depends on 14)

The method of claim 14, wherein said cells express a marker selected from the group consisting of CD90, CD105, CD73 and CD29.

### Claim 16 (depends on 1)

The method of claim 1, wherein treating the wound comprises treating delayed wound healing.

### Claim 17 (depends on 16)

The method of claim 16, wherein the wound is an ulcer.

### Claim 18 (depends on 17)

The method of claim 17, wherein the ulcer wound is to the skin.

### Claim 19 (depends on 3)

The method of claim 3, wherein the wound to the skin is an ulcer.

### Claim 20 (depends on 1)

The method of claim 1, wherein the undifferentiated placenta-derived adherent stromal cells are non-autologous to the subject.

### Claim 21

A method of preparing cells for treating a wound in a subject in need thereof, the method comprising expanding placenta-derived adherent stromal cells in culture, wherein when the culture-expanded placenta-derived adherent stromal cells are subsequently systemically administered in a liquid suspension to a subject in a therapeutically effective amount they treat a wound in the subject.

### Claim 22 (depends on 21)

The method of claim 21, wherein the culture is a 3D culture.

### Claim 23 (depends on 22)

The method of claim 22, wherein said placenta-derived adherent stromal cells are non-autologous to the subject.

### Claim 24

A method of preparing cells for treating a wound in a subject in need thereof, the method comprising expanding non-autologous placenta-derived adherent stromal cells in three-dimensional culture, wherein when the culture-expanded placenta-derived adherent stromal cells are subsequently systemically administered in a liquid suspension to the subject in a therapeutically effective amount they treat a wound in the subject.
