Methods and Compositions for Treatment of Bone Defects with Placental Cell Populations

• US 20080213228A1
• Filed: 10/23/2007
• Published: 09/04/2008
• Est. Priority Date: 10/23/2006
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Hariri, Robert J., Ye, Qian, Wang, Jia-Lun, Edinger, James W., Labazzo, Kristen S., Pereira, Marian, Abramson, Sascha Dawn
• Granted Patent: US 8,562,972 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/42 Organic phosphate, e.g. beta glycerophosphate
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2506/025 from extra-embryonic cells, e.g. trophoblast, placenta
• CPC Class Codes: C12N 2506/03 from non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 2533/18 Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0654 Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources

Abstract

Provided herein are methods of using adherent placental stem cells and placental stem cell populations, and methods of culturing, proliferating and expanding the same. Also provided herein are methods of differentiating the placental stem cells. Further provided herein are methods of using the placental stem cells to formulate implantable or injectable compositions suitable for administration to a subject. Still further provided herein are provides methods for treating bone defects with stem cells and compositions comprising stem cells.

Claims

1. A method of producing osteogenic cells with the ability to mineralize matrix, comprising culturing a plurality of nonadherent stem cells a population of isolated stem cells, under conditions in which said stem cells differentiate into osteogenic cells, said culturing being for a time sufficient for said osteogenic cells to produce detectable amounts of mineralized matrix rich in calcium or phosphate.

2. The method of claim 1, comprising contacting said cells with dexamethasone or ascorbic acid.

3. A method for formulating a matrix, comprising combining a population of nonadherent CD34⁺ and CD44⁻

placental stem cells with an implantable scaffolding substrate that is β

-tricalcium phosphate substrate, a β

-tricalcium phosphate-collagen substrate, a collagen substrate, a calcium phosphate substrate, a mineralized human placental collagen substrate, a hyaluronic acid substrate, or a ceramic substrate.

4. A method for formulating an injectable composition, comprising combining a population of nonadherent CD34+, CD44−

placental stem cells with injectable hyaluronic acid or collagen.

5. A method for treating bone defects in a subject, comprising administering to a subject in need thereof an implantable or injectable composition comprising a population of nonadherent stem cells, thereby treating the bone defect in the subject.

6. The method of claim 5, wherein the bone defect is an osteolytic lesion associated with a cancer, a bone fracture, or a spine in need of fusion.

7. The method of claim 6, wherein the osteolytic lesion is associated with multiple myeloma, bone cancer, or metastatic cancer.

8. The method of claim 6, wherein the bone fracture is a non-union fracture.

9. The method of claim 5, wherein the implantable composition is surgically implanted.

10. The method of claim 5, wherein an injectable composition comprising a population of nonadherent stem cells is administered to the subject.

11. The method of claim 5, wherein the injectable composition is surgically administered to the region of the bone defect.

12. The method of claim 5, wherein the injectable composition is systemically administered.

13. A method for formulating an matrix, comprising combining a population of stem cells with an implantable scaffolding substrate, wherein said stem cells are CD200⁺ or HLA-G⁺, or CD34⁺ and CD44⁻

.

14. A method for formulating an injectable composition, comprising combining a population of stem cells with injectable hyaluronic acid or collagen, wherein said stem cells are CD200⁺ or HLA-G⁺, or are CD34⁺ and CD44⁻

.

15. A method for treating bone defects in a subject, comprising administering to a subject in need thereof an implantable or injectable composition comprising a population of stem cells, wherein said stem cells are CD200⁺ or HLA-G⁺, or are CD34⁺ and CD44⁻

, thereby treating the bone defect in the subject.

16. The method of claim 15, wherein the bone defect is an osteolytic lesion associated with multiple myeloma, bone cancer, or metastic cancer, a bone fracture, or a spine in need of fusion.

17. The method of claim 15, wherein an implantable composition comprising a population of nonadherent stem cells is administered to the subject.

18. The method of claim 17, wherein the implantable composition is surgically implanted.

19. The method of claim 15, wherein an injectable composition comprising a population of nonadherent stem cells is administered to the subject.

20. The method of claim 19, wherein the injectable composition is systemically administered.