Methods and compositions for treatment of bone defects with placental cell populations

• US 10,105,399 B2
• Filed: 04/07/2016
• Issued: 10/23/2018
• Est. Priority Date: 10/23/2006
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Celularity, Inc.
• Inventors: Edinger, James W., Hariri, Robert J., Wang, Jia-Lun, Ye, Qian, Labazzo, Kristen S., Pereira, Marian, Abramson, Sascha Dawn
• Primary Examiner(s): Kim, Taeyoon
• Application Number:
  US15/093,185
• Publication Number:
  US 20170056452A1
• Time in Patent Office: 929 Days
• 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 for treating a bone defect in a subject, wherein said bone defect is an osteolytic lesion associated with multiple myeloma, bone cancer, or metastatic cancer characterized by bone metastases, comprising administering to a subject in need thereof an implantable or injectable composition comprising a population of placental stem cells,

wherein said population is predominantly CD34⁻

, CD10⁺, CD105⁺, and CD200⁺;

wherein said stem cells express genes at a detectably higher level than an equivalent number of bone marrow-derived mesenchymal stem cells (BM-MSCs);

and wherein said genes comprise CPA4, TCF21, VTN, B4GALT6, FLJ10781, or NUAK1;

thereby treating the bone defect in the subject.

2. The method of claim 1, wherein said placental stem cells have been passaged at least six times.

3. The method of claim 1, wherein said population is predominantly CD34⁻

, CD45⁻

, CD10⁺, CD90⁺, CD105⁺, and CD200⁺.

4. The method of claim 1, wherein said placental stem cells comprise at least 70% of cells in said composition.

5. The method of claim 1, wherein said placental stem cells comprise at least 90% of cells in said composition.

6. The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with multiple myeloma.

7. The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with bone cancer.

8. The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with metastatic cancer.

9. The method of claim 1, wherein said placental stem cells are cells from a placental stem cell bank.

10. The method of claim 1, wherein said composition is formulated as a suspension or liquid that can be administered intravenously.

11. The method of claim 1, wherein said composition comprises 5×

10⁶ said placental stem cells per milliliter.

12. The method of claim 1, wherein said composition comprises an implantable substrate or matrix.

13. The method of claim 1, wherein said composition comprises human serum albumin (HSA) and dextran-40.

14. The method of claim 1, wherein said placental stem cells are autologous to said subject.

15. The method of claim 1, wherein said placental stem cells have been cryopreserved.

16. The method of claim 1, wherein said population is predominantly CD73⁺.

17. The method of claim 16, wherein at least 80% of the placental stem cells in said population are CD73⁺, CD105⁺, and CD200⁺.

18. The method of claim 16, wherein at least 90% of the placental stem cells in said population are CD73⁺, CD105⁺, and CD200⁺.

19. The method of claim 1, wherein said population has been passaged at least three times.

20. The method of claim 19, wherein said population has been passaged no more than ten times.