# US 2019/0167728 A1 · In Vivo and Ex Vivo Expansion of Hematopoietic Stem Cells With a Targeted Combination of Clinically Tested, FDA Approved Drugs

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- Number: US 2019/0167728 A1
- Document ID: US20190167728A1
- Status: Published application
- Kind: A1
- Application number: 16/263,060
- Filed: 2019-01-31
- Published: 2019-06-06
- Earliest claimed: 2010-04-12
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Peter S. Klein; Jian Huang
- Web page: https://patentgrep.com/patent/US20190167728A1

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/06: Antianaemics
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C12N 5/0647: {Haematopoietic stem cells; Uncommitted or multipotent progenitors}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- C12N 2500/12: Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
- C12N 2500/30: Organic components
- C12N 2501/04: Immunosuppressors, e.g. cyclosporin, tacrolimus
- C12N 2501/20: Cytokines; Chemokines
- C12N 2501/415: Wnt; Frizzeled
- C12N 2501/727: Kinases (EC 2.7.)
- C12N 2510/00: Genetically modified cells
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides a therapeutic approach to maintain and expand HSCs in vivo using currently available medications that target GSK-3 and mTOR. The present invention also provides a system and method for the ex vivo culturing of HSCs, where an mTOR inhibitor is combined with a GSK-3 inhibitor within the culturing conditions.

## Claims

### Claim 1

A culturing medium for expanding and maintaining a hematopoietic stem cell (HSC), comprising at least one glycogen synthase kinase-3 (GSK-3) inhibitor and at least one mammalian target of rapamycin (mTOR) inhibitor.

### Claim 2 (depends on 1)

The culturing medium of claim 1, wherein the culturing medium is capable of maintaining the multipotentiality of an HSC when the HSC is maintained or expanded in the culturing medium.

### Claim 3 (depends on 1)

The culturing medium of claim 1, further comprising at least one cytokine.

### Claim 4 (depends on 1)

The culturing medium of claim 1, further comprising a promotion factor.

### Claim 5 (depends on 1)

The culturing medium of claim 1, wherein the GSK-3 inhibitor is lithium, or a salt thereof.

### Claim 6 (depends on 1)

The culturing medium of claim 1, wherein the mTOR inhibitor is rapamycin.

### Claim 7 (depends on 1)

The culturing medium of claim 1, further comprising a culture medium component selected from the group consisting of: inorganic salts, carbohydrates, hormones, essential amino acids, vitamins, RPMI 1640, HEPES, FCS, antibiotics, and combinations thereof.

### Claim 8 (depends on 1)

The culturing medium of claim 1, wherein the medium is configured to achieve an HCS expansion of about 1-fold expansion to about 200-fold expansion.