# US 2017/0280692 A1 · Organ regeneration method utilizing blastocyst complementation

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- Number: US 2017/0280692 A1
- Document ID: US20170280692A1
- Status: Published application
- Kind: A1
- Application number: 15/375,982
- Filed: 2016-12-12
- Published: 2017-10-05
- Earliest claimed: 2007-02-22
- Assignees: The University of Tokyo
- Applicants: The University of Tokyo
- Inventors: Hiromitsu NAKAUCHI; Toshihiro KOBAYASHI; Younsu LEE; Joichi USUI; Tomoyuki YAMAGUCHI; Sanae HAMANAKA
- Web page: https://patentgrep.com/patent/US20170280692A1

## CPC

- A01K 67/0271: Chimeric vertebrates, e.g. comprising exogenous cells
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A01K 2207/20: Animals treated with compounds which are neither proteins nor nucleic acids
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)

## Abstract

An object of the present invention is to produce a mammalian organ having a complicated cellular composition composed of multiple kinds of cells, such as kidney, pancreas, thymus and hair, in the living body of a non-human animal. The inventors of the present invention applied the chimeric animal assay described above, to a novel solid organ production method. More specifically, the inventors has shown that a model mouse which is deficient of kidney, pancreas, thymus or hair due to the dysfunction of the metanephric mesenchyme that is differentiated into most of an adult kidney, is rescued by blastocyst complementation by the chimeric animal assay, and whereby a kidney, a pancreas, thymus or hair can be newly produced.

## Claims

### Claim 1

A method for producing a target organ in the living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in the development stage, the target organ being derived from an allogeneic and/or xenogeneic mammal that is an individual different from the non-human mammal, the method comprising:
a) preparing a cell derived from the allogeneic and/or xenogeneic mammal;
b) transplanting the cell into a blastocyst stage fertilized egg of the non-human mammal;
c) developing the fertilized egg in the womb of a non-human surrogate parent mammal to obtain a litter; and
d) obtaining the target organ from an individual of the litter.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said cell is an embryonic stem cell (ES cell) or an induced pluripotent stem cell (iPS cell).

### Claim 3 (depends on 1)

The method according to claim 1, wherein said cell is derived from a mouse.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said organ to be produced is selected from a kidney, a pancreas, thymus and hair.

### Claim 5 (depends on 1)

The method according to claim 1, wherein said non-human mammal is a mouse.

### Claim 6 (depends on 1)

The method according to claim 1, wherein said mouse is a Sall1 knockout mouse, a Pdx-1 knockout mouse, or a nude mouse.

### Claim 7 (depends on 1)

The method according to claim 1, wherein said target organ is completely derived from said allogeneic and/or xenogeneic mammal.

### Claim 8 (depends on 1)

The method according to claim 1, wherein said cell is derived from a rat.

### Claim 9 (depends on 1)

The method according to claim 1, wherein said cell and said non-human mammal are heterologous to each other.

### Claim 10 (depends on 1)

The method according to claim 1, wherein said cell is from a rat, and said non-human mammal is from a mouse.

### Claim 11

A non-human mammal having an abnormality associated with a lack of development of a target organ in the development stage, produced according to a method comprising:
a) preparing a cell derived from an allogeneic and/or xenogeneic mammal that is an individual different from the non-human mammal;
b) transplanting the cell into a blastocyst stage fertilized egg of the non-human mammal; and
c) developing the fertilized egg in the womb of a non-human surrogate parent mammal to obtain a litter.

### Claim 12

Use of a non-human mammal having an abnormality associated with a lack of development of a target organ in the development stage, for the generation of the target organ.

### Claim 13

A set for producing a target organ, the set comprising:
A) a non-human mammal having an abnormality associated with a lack of the target organ development in the development stage; and
B) a cell derived from an allogeneic and/or xenogeneic mammal of the same species as the non-human mammal.

### Claim 14 (depends on 13)

The set according to claim 13, wherein said cell and said non-human mammal are heterologous to each other.

### Claim 15 (depends on 1)

The method according to claim 1, wherein said cell is from a rat, and said non-human mammal is from a mouse.
