# US 11,512,282 B2 · Enhanced placental stem cells and uses thereof

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- Number: US 11,512,282 B2
- Document ID: US11512282B2
- Status: Granted
- Kind: B2
- Application number: 16/384,857
- Filed: 2019-04-15
- Published: 2021-08-05
- Granted: 2022-11-29
- Earliest claimed: 2013-03-14
- Assignees: Celularity Inc.
- Applicants: Celularity Inc.
- Inventors: Stewart Abbot; Katarzyna Karasiewicz-Mendez; Robert J Hariri; Xiaokui Zhang
- Web page: https://patentgrep.com/patent/US11512282B2

## CPC

- C12N 5/0605: {Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly}
- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2501/65: MicroRNA
- 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)

## Abstract

Provided herein are placental stem cells that exhibit increased survival (“enhanced placental stem cells”), compositions comprising such placental stem cells, and methods of using such placental stem cells and compositions.

## Claims

### Claim 1

An isolated placental stem cell, wherein said placental stem cell has been modified to comprise or express miR-29a, and wherein said placental stem cell demonstrates increased survival relative to corresponding unmodified placental stem cells when cultured under one or more conditions that cause cell death.

### Claim 2 (depends on 1)

The isolated placental stem cell of claim 1, wherein said placental stem cell expresses at least one survival-associated gene at a decreased level as compared to the expression of the same survival-associated gene in a corresponding unmodified placental stem cell.

### Claim 3 (depends on 2)

The isolated placental stem cell of claim 2, wherein said survival-associated gene is ADAMTS9, BACE1, BCL2, CAV2, CD276, CDC42, CDK6, COL3A1, COL4A1, COL4A2, CPEB3, TRIM63, CXXC6/TET1, DIABLO, DNMT3A, DNMT3B, FGA, IMPDH1, INSIG1, KREMEN2, LPL, MCL1, PIK3R1, PPM1D, SPARC.

### Claim 4 (depends on 1)

The isolated placental stem cell of claim 1, wherein said miR-29a causes said placental cell to express Cyclin D3 and/or Cyclin E at an increased level as compared to a corresponding unmodified placental stem cell.

### Claim 5 (depends on 1)

The isolated placental stem cell of claim 1, wherein said placental stem cell exhibits (i) decreased expression of caspase 3/7, (ii) increased mitochondrial membrane potential, and/or (iii) increased metabolic activity when cultured under one or more conditions that cause cell death as compared to corresponding unmodified placental stem cells cultured under the same condition(s).

### Claim 6 (depends on 1)

An isolated population of cells, wherein at least 50% of the cells in said population are the cells of claim 1.

### Claim 7 (depends on 1, 6)

The isolated population of cells of claim 6, wherein at least 80% of the cells in said population of cells are the cells of claim 1.

### Claim 8 (depends on 6)

The population of cells of claim 6, wherein said placental stem cells in said population are CD10+, CD34−, CD105+, CD200+placental stem cells.

### Claim 9 (depends on 1)

A composition comprising the isolated placental stem cell of claim 1.

### Claim 10 (depends on 1)

The placental stem cell of claim 1, wherein said placental stem cell is a CD10+, CD34−, CD105+, CD200+placental stem cell.

### Claim 11 (depends on 1)

The composition of claim 1, wherein said placental stem cells are CD10+, CD34−, CD105+, CD200+placental stem cells.

### Claim 12

A method of producing placental stem cells that comprise or express miR-29a, wherein said placental stem cells demonstrate increased survival relative to corresponding unmodified placental stem cells when cultured under one or more conditions that cause cell death, said method comprising contacting a population of placental stem cells with an effective amount of miR-29a, such that said placental stem cells, after having been contacted with said miR-29a express Cyclin D3 and/or Cyclin E at an increased level as compared to a corresponding number of unmodified placental stem cells not contacted with said miR-29a.

### Claim 13 (depends on 12)

An isolated placental stem cell or population thereof produced by the method of claim 12.

### Claim 14 (depends on 12)

A composition comprising an isolated placental stem cell produced by the method of claim 12.

### Claim 15 (depends on 12)

The method of claim 12, wherein said placental stem cells are CD10+, CD34−, CD105+, CD200+placental stem cells.