Cell compositions derived from dedifferentiated reprogrammed cells

• US 9,982,235 B2
• Filed: 07/07/2015
• Issued: 05/29/2018
• Est. Priority Date: 04/22/2009
• Status: Active Grant

• Current Assignee: Viacyte Incorporated (Vertex Pharmaceuticals Incorporated)
• Original Assignee: Viacyte Incorporated (Vertex Pharmaceuticals Incorporated)
• Inventors: Agulnick, Alan D., Kelly, Olivia, Ohi, Yuki, Robins, Allan, Schulz, Thomas
• Primary Examiner(s): Fox, Allison M
• Application Number:
  US14/793,326
• Publication Number:
  US 20160369239A1
• Time in Patent Office: 1,057 Days
• Field of Search: None
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/117 Keratinocyte growth factors (KGF-1, i.e. FGF-7; KGF-2, i.e. FGF-12)
• CPC Class Codes: C12N 2501/16 Activin; Inhibin; Mullerian inhibiting substance
• CPC Class Codes: C12N 2501/195 Heregulin, neu differentiation factor
• CPC Class Codes: C12N 2501/385 of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
• CPC Class Codes: C12N 2501/41 Hedgehog proteins; Cyclopamine (inhibitor)
• CPC Class Codes: C12N 2501/415 Wnt; Frizzeled
• CPC Class Codes: C12N 2501/727 Kinases (EC 2.7.)
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 2506/45 from artificially induced pluripotent stem cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Disclosed herein are cell culture compositions, for example, pancreatic cell culture compositions, derived from dedifferentiated human reprogrammed pluripotent stem cells, such as induced pluripotent stem (iPS) cells, and methods for producing and using such cell culture compositions.

Claims

1. A pancreatic progenitor cell population comprising endocrine cell and non-endocrine cell subpopulations, wherein the cell population is derived from dedifferentiated human reprogrammed pluripotent stein cells in a medium comprising an effective amount of growth factor, wherein the growth factor is an epidermal growth factor (EGF) family ligand or a fibroblast growth factor, and at least at least 30% of the cell population is the non-endocrine cell subpopulation.

2. The cell population of claim 1, wherein the non-endocrine cell subpopulation expresses NKX6.1, but does not express Chromogranin A and wherein the endocrine cell subpopulation expresses Chromogranin A.

3. The cell population of claim 1, wherein the EGF family ligand comprises a heregulin isoform.

4. The cell population of claim 3, wherein the heregulin isoform comprises heregulin-1β

, heregulin-1, heregulin-2, heregulin-3 or heregulin-4.

5. The cell population of claim 1, wherein the pancreatic progenitor cell population comprises PDX1-positive pancreatic endoderm cells.

6. The cell population of claim 1, wherein the pancreatic progenitor cell population is encapsulated and can be transplanted in vivo.

7. The cell population of claim 6, wherein the transplanted pancreatic progenitor cell population matures in vivo to insulin producing cells.

8. The cell population of claim 1, wherein the pancreatic progenitor cell population is encapsulated in a semipermeable device comprising a semi-permeable membrane.

9. The cell population of claim 8, wherein the semi-permeable device comprises at least one cell encapsulating chamber.

10. The cell population of claim 9, wherein the at least one cell encapsulating chamber comprises at least one seal.

11. The cell population of claim 1, wherein the dedifferentiated human reprogrammed pluripotent stem cells are induced pluripotent stein cells.

12. The cell population of claim 1, wherein the pancreatic progenitor cell population is encapsulated in a device comprising a sealed edge, a cell encapsulating chamber;

a partition seal within the cell encapsulating chamber, wherein the partition seal within the cell encapsulating chamber does not increase the surface area of the chamber.

13. The cell population of claim 1, wherein the fibroblast growth factor comprises FGF1, FGF2, FGF3, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23.

14. The cell population of claim 1, wherein the pancreatic progenitor cell population is encapsulated in a device comprising a semi-permeable membrane,

wherein the semi-permeable membrane comprises a synthetic material, wherein the synthetic material is polysulfone (PSF), nano-fiber mats, polyimide, tetrafluoroethylene/polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyacrylonitrile, polyethersulfone, acrylic resin, cellulose acetate, cellulose nitrate, polyamide, or hydroxylpropyl methyl cellulose (HPMC).

15. The cell population of claim 8, wherein the semipermeable device comprises a perforated semi-permeable membrane.