# US 7,745,113 B2 · Use of islet 1 as a marker for isolating or generating stem cells

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- Number: US 7,745,113 B2
- Document ID: US7745113B2
- Status: Granted
- Kind: B2
- Application number: 10/544,053
- Filed: 2004-02-02
- Published: 2006-11-02
- Granted: 2010-06-29
- Earliest claimed: 2003-01-31
- Assignees: The Regents of the University of California
- Inventors: Sylvia M. Evans; Ju Chen; Chenleng Cai; Alessandra Moretti; Kenneth R. Chien; Karl-Ludwig Laugwitz
- Web page: https://patentgrep.com/patent/US7745113B2

## CPC

- C12N 5/0662: {Stem cells}
- C12N 5/0657: {Cardiomyocytes; Heart cells}
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/56966: {Animal cells}
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/415: Wnt; Frizzeled
- C12N 2502/99: genetically modified cells
- C12Q 2600/158: Expression markers
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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 present invention provides in vitro methods of expansion and propagation of undifferentiated progenitor cells and more specifically undifferentiated progenitor cells containing Islet1, a marker apparently unique to proliferating cardiac stem cells. Methods are described for isolation of stem cell populations as well as for provoking expansion and propagation of undifferentiated progenitor cells without differentiation, to provide cardiac repair or improve cardiac function, for example.

## Claims

### Claim 1

An in vitro method of culturing and expanding a cell population of undifferentiated mammalian cardiac progenitor cells substantially free of differentiated cells, comprising:
culturing isolated undifferentiated mammalian progenitor cells that express Islet1 on a feeder layer of species-specific cardiac fibroblasts or conditioned medium from cardiac fibroblasts, thereby culturing and expanding a cell population of undifferentiated mammalian cardiac progenitor cells substantially free of differentiated cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the undifferentiated progenitor cells are derived from mammalian non-myocyte cells.

### Claim 3 (depends on 2)

The method of claim 2, wherein the mammalian non-myocyte cells are rat, mouse or human cells.

### Claim 4 (depends on 1)

The method of claim 1, wherein the mammalian undifferentiated progenitor cells are derived from mammalian adult progenitor cells.

### Claim 5 (depends on 4)

The method of claim 4, wherein the mammalian adult progenitor cells are derived from cardiac tissue of a rat, mouse or human.

### Claim 6

An in vitro method of culturing and expanding a cell population of undifferentiated mammalian cardiac progenitor cells substantially free of differentiated cells, comprising:
culturing isolated undifferentiated mammalian progenitor cells that express Islet1 and Nkx2.5 on a feeder layer of species-specific cardiac fibroblasts or conditioned medium from cardiac fibroblasts, thereby culturing and expanding a cell population of undifferentiated mammalian cardiac progenitor cells substantially free of differentiated cells.

### Claim 7 (depends on 6)

The method of claim 6, wherein the mammalian undifferentiated progenitor cells are derived from mammalian non-myocyte cells.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mammalian non-myocyte cells are rat, mouse or human cells.

### Claim 9

An in vitro method of culturing and expanding a cell population of undifferentiated mammalian cardiac adult stem cells substantially free of differentiated cells, comprising:
culturing said isolated undifferentiated mammalian adult stem cells that express Islet1 on a feeder layer of species-specific cardiac fibroblasts or conditioned medium from cardiac fibroblasts, thereby culturing and expanding a cell population of undifferentiated mammalian cardiac adult stem cells.

### Claim 10 (depends on 9)

The method of claim 9, wherein the undifferentiated mammalian adult stem cells are derived from mammalian non-myocyte cells.

### Claim 11 (depends on 10)

The method of claim 10, wherein the mammalian non-myocyte cells are rat, mouse or human cells.

### Claim 12 (depends on 9)

The method of claim 9, wherein the mammalian adult stem cells are postnatal stem cells.

### Claim 13 (depends on 9)

The method of claim 9, wherein the mammalian adult stem cells are multipotent stem cells.

### Claim 14 (depends on 9)

The method of claim 9, wherein the mammalian adult stem cells are mesenchymal stem cells.

### Claim 15 (depends on 9)

The method of claim 9, wherein the mammalian adult stem cells further express Nkx2.5.