# US 2014/0154326 A1 · Micro organ comprising mesenchymal and epithelial cells

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- Number: US 2014/0154326 A1
- Document ID: US20140154326A1
- Status: Published application
- Kind: A1
- Application number: 14/235,257
- Filed: 2012-07-23
- Published: 2014-06-05
- Earliest claimed: 2011-07-27
- Assignees: University of Durham
- Inventors: Aihua Guo; Colin Albert Buchanan Jahoda
- Web page: https://patentgrep.com/patent/US20140154326A1

## CPC

- C12N 5/0698: {Skin equivalents}
- A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- G01N 33/5082: {Supracellular entities, e.g. tissue, organisms}
- C12N 2502/092: hair cells
- C12N 2502/094: keratinocytes
- C12N 2502/1323: Adult fibroblasts
- C12N 2503/06: Screening or testing on artificial skin
- C12N 2513/00: 3D culture
- 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)
- 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)

## Abstract

The invention provides a micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are mesenchymal cells and the cells of the outer layer are epithelial cells or wherein the cells of the core group are epithelial cells and the cells of the outer layer are mesenchymal cells, and wherein the core group of cells is at least partially encapsulated by the outer layer of cells.

## Claims

### Claim 1

A micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are mesenchymal cells and the cells of the outer layer are epithelial cells, wherein the core group of cells is at least partially encapsulated by the outer layer of cells.

### Claim 2

A micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are epithelial cells and the cells of the outer layer are mesenchymal cells, wherein the core group of cells is at least partially encapsulated by the outer layer of cells.

### Claim 3

The composite according to any one of the preceding claim, wherein the mesenchymal cells and/or the epithelial cells are derived from more than one cell source.

### Claim 4

The composite according to any one of the preceding claims, wherein the mesenchymal cells are dermal cells, and wherein the epithelial cells are epidermal cells.

### Claim 5 (depends on 4)

The composite according to claim 4, wherein said epidermal cells are keratinocytes

### Claim 6

The composite according to any of the preceding claims, wherein said mesenchymal core and epithelial outer layer interact so as to form a basement membrane.

### Claim 7

The composite according to any one of the preceding claims, wherein the core group of cells is fully encapsulated by the outer layer of cells.

### Claim 8

The composite according to any one of the preceding claim, wherein the composite is in the form of a spherical particulate.

### Claim 9 (depends on 8)

The composite according to claim 8, wherein the spherical particulate has a size between 40 and 500 microns.

### Claim 10

A composite according to any one of the preceding claims for use as a medicament.

### Claim 11

A composite according to any one of the preceding claims for use in skin wound healing.

### Claim 12 (depends on 11)

The composite according to claim 11, wherein the dermal cells are dermal fibroblasts and the epithelial cells are keratinocytes.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A composite according to any one of claims 1 to 9 for use in treating alopecia.

### Claim 14 (depends on 13)

The composite according to claim 13, wherein the dermal cells are follicular dermal cells and the epithelial cells are outer root sheath keratinocytes.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A pharmaceutical composition comprising a composite according to any one of claims 1 to 9 together with a pharmaceutically acceptable carrier.

### Claim 16 (depends on 11, 12, 13, 14, 15)

The composite for use according to any one of claims 11 to 14 or the pharmaceutical composition according to claim 15, wherein said composite or composition is prepared for topical administration.

### Claim 17

A method of producing a micro-organ cell composite, comprising:
a) growing disaggregated mesenchymal cells in a hanging drop culture to form an aggregate core of cells; and
b) adding epithelial cells to the aggregate core of cells,
wherein the epithelial cells grow to form an outer layer on the aggregate core of cells.

### Claim 18

A method of producing a micro-organ cell composite, comprising:
a) growing disaggregated epithelial cells in a hanging drop culture to form an aggregate core of cells; and
b) adding mesenchymal cells to the aggregate core of cells,
wherein the mesenchymal cells grow to form an outer layer on the aggregate core of cells.

### Claim 19 (depends on 17, 18)

The method according to claim 17 or claim 18, wherein the mesenchymal cells are dermal cells, and wherein the epithelial cells are epidermal cells.

### Claim 20 (depends on 19)

The method according to claim 19, wherein said epidermal cells are keratinocytes.

### Claim 21 (depends on 17, 18)

The method according to any one of claims 17 to 18, wherein the aggregate core of cells and the outer layer establish a basement membrane, preferably in less than 2 days, less than 3 days, less than 4 days, less than 5 days or less than 6 days.

### Claim 22 (depends on 17, 18, 19, 20)

The method of according to any one of claims 17 to 20, wherein the cells of the composite are viable for about 2 weeks or more, or about 3 weeks or more.

### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

An in vitro model for studying a skin disease or disorder comprising the composite according to any one of claims 1 to 9.

### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

Use of a composite according to any one of claims 1 to 9 as an in vitro skin model.

### Claim 25 (depends on 24)

Use according to claim 24, wherein said skin model is a skin disease or disorder model.

### Claim 26 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A method of screening an agent for the treatment of a skin disease or disorder comprising:
a) providing a composite according to any one of claims 1 to 9;
b) exposing said composite to an agent; and
c) determining whether the agent has a therapeutic effect on the composite.

### Claim 27 (depends on 23, 25, 26)

The in vitro model according to claim 23, the use according to claim 25 or the method according to claim 26, wherein the skin disease or disorder is a keloid, a tumour, or a wound.

### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A method of screening for any molecular or chemical agent:
a) providing a composite according to any one of claims 1 to 9;
b) exposing said composite to an agent; and
c) determining whether the agent has a toxic effect on the composite, or affects cell growth or viability, or alters gene expression in the composite cells.

### Claim 29 (depends on 17, 18, 19, 20, 21, 22)

A micro-organ cell composite obtainable by the method according to any one of claims 17 to 22.

### Claim 30

A micro-organ cell composite substantially as described herein with reference to the accompanying drawings.

### Claim 31

A method of producing micro-organ cell composite as described herein with reference to the accompanying drawings.