# US 2008/0187514 A1 · Methods and Compositions for the Repair and/or Regeneration of Damaged Myocardium

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- Number: US 2008/0187514 A1
- Document ID: US20080187514A1
- Status: Published application
- Kind: A1
- Application number: 11/961,537
- Filed: 2007-12-20
- Published: 2008-08-07
- Earliest claimed: 2000-07-31
- Assignees: New York Medical College
- Inventors: Piero Anversa
- Web page: https://patentgrep.com/patent/US20080187514A1

## CPC

- C12N 5/0647: {Haematopoietic stem cells; Uncommitted or multipotent progenitors}
- A01K 67/0271: Chimeric vertebrates, e.g. comprising exogenous cells
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- C12N 2501/12: Hepatocyte growth factor [HGF]
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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

Methods, compositions, and kits for repairing damaged myocardium and/or myocardial cells including the administration of stem cells, such as adult stem cells, optionally with cytokines are disclosed and claimed.

## Claims

### Claim at position 1

1-160. (canceled)

### Claim 161

A method for restoring functional and structural integrity to damaged myocardium in a patient in need thereof comprising:
(a) isolating adult hematopoietic stem cells from a bone marrow specimen; and
(b) administering an effective dose of said isolated adult hematopoietic stem cells to the border region of said damaged myocardium in the patient's heart, wherein the functional and structural integrity of the damaged myocardium is restored following stem cell administration.

### Claim 162 (depends on 161)

The method of claim 161, wherein the isolated adult hematopoietic stem cells are lineage negative.

### Claim 163 (depends on 162)

The method of claim 162, wherein the isolated adult hematopoietic stem cells are c-kit positive.

### Claim 164 (depends on 161)

The method of claim 161, wherein the adult hematopoietic stem cells migrate into the damaged myocardium.

### Claim 165 (depends on 161)

The method of claim 161, wherein the adult hematopoietic stem cells differentiate into myocytes, endothelial cells, and smooth muscle cells.

### Claim 166 (depends on 165)

The method of claim 165, wherein the differentiated adult hematopoietic stem cells proliferate.

### Claim 167 (depends on 165)

The method of claim 165, wherein the differentiated adult hematopoietic stem cells assemble into myocardium and a coronary artery.

### Claim 168 (depends on 165)

The method of claim 165, wherein the differentiated adult hematopoietic stem cells assemble into myocardium and an arteriole.

### Claim 169 (depends on 165)

The method of claim 165, wherein the differentiated adult hematopoietic stem cells assemble into myocardium and a capillary.

### Claim 170 (depends on 161)

The method of claim 161, wherein the bone marrow specimen is obtained from the patient to which the isolated adult hematopoietic stem cells are administered.

### Claim 171 (depends on 161)

The method of claim 161, wherein the isolated adult hematopoietic stem cells are administered by injection.

### Claim 172 (depends on 171)

The method of claim 171, wherein the injection is intramyocardial.

### Claim 173 (depends on 171)

The method of claim 171, wherein the injection is trans-epicardial or trans-endocardial.

### Claim 174 (depends on 161)

The method of claim 161, wherein the isolated adult hematopoietic stem cells are administered by a catheter.

### Claim 175 (depends on 161)

The method of claim 161, wherein the effective dose of isolated adult hematopoietic stem cells is from about 2×104 to 1×105.

### Claim 176 (depends on 161)

The method of claim 161, further comprising the administration of an effective dose of one or more cytokines.

### Claim 177 (depends on 176)

The method of claim 176, wherein the one or more cytokines is selected from the group consisting of:
(a) stem cell factor;
(b) granulocyte-colony stimulating factor;
(c) stromal cell-derived factor-1;
(d) interleukin-3;
(e) granulocyte-macrophage colony stimulating factor;
(f) macrophage colony stimulating factor;
(g) vascular endothelial cell growth factor;
and combinations thereof.

### Claim 178 (depends on 177)

The method of claim 177, wherein the administered cytokines are stem cell factor and granulocyte colony stimulating factor.

### Claim 179 (depends on 176)

The method of claim 176, wherein the effective dose of one or more cytokines is from 50 μg/kg to 500 μg/kg.

### Claim 180 (depends on 176)

The method of claim 176, wherein the effective dose of one or more cytokines is administered in multiple administrations.

### Claim 181 (depends on 180)

The method of claim 180, wherein the multiple administrations are given over the course of several days following the administration of the isolated adult hematopoietic stem cells.

### Claim 182 (depends on 176)

The method of claim 176, wherein the effective dose of one or more cytokines is administered systemically to the patient.

### Claim 183 (depends on 182)

The method of claim 182, wherein the systemic administration is subcutaneous or intravenous injection.

### Claim 184 (depends on 176)

The method of claim 176, wherein the administration of one or more cytokines stimulates the patient's resident hematopoietic stem cells causing them to mobilize into the bloodstream.

### Claim 185

A method for restoring functional and structural integrity to damaged myocardium in a patient in need thereof comprising:
(a) isolating adult hematopoietic stem cells from a bone marrow specimen;
(b) culturing said isolated adult hematopoietic stem cells in vitro, wherein said adult hematopoietic stem cells proliferate and differentiate into myocytes, endothelial cells, and smooth muscle cells, thereby forming cardiac structures; and
(b) implanting said cardiac structures formed in vitro into said damaged myocardium in the patient's heart, wherein the implanted cardiac structures restore functional and structural integrity to the damaged myocardium.

### Claim 186 (depends on 185)

The method of claim 185, wherein the cardiac structures include myocardium, coronary arteries, arterioles, and/or capillaries.

### Claim 187

A method for restoring functional and structural integrity to damaged myocardium in a patient in need thereof comprising the administration of an effective dose of one or more cytokines selected from the group consisting of:
a. a stem cell factor;
b. a granulocyte-colony stimulating factor;
c. a stromal cell-derived factor-1;
d. an interleukin-3;
e. a granulocyte-macrophage colony stimulating factor;
f. a macrophage colony stimulating factor;
g. a vascular endothelial cell growth factor;
and combinations thereof, wherein the functional and structural integrity of the damaged myocardium is restored following cytokine administration.

### Claim 188 (depends on 187)

The method of claim 187, wherein the administered cytokines are stem cell factor and granulocyte colony stimulating factor.