CELL COMPOSITIONS DERIVED FROM DEDIFFERENTIATED REPROGRAMMED CELLS

• US 20160369239A1
• Filed: 07/07/2015
• Published: 12/22/2016
• 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
• Granted Patent: US 9,982,235 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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

1-16. -16. (canceled)

17. An encapsulated pancreatic progenitor cell population derived from dedifferentiated human reprogrammed pluripotent stem cells.

18. The cell population of claim 17, wherein the pancreatic progenitor cell population comprises endocrine cell and non-endocrine cell subpopulations.

19. The cell population of claim 18, wherein the non-endocrine cell subpopulation expresses NKX6.1, but does not express Chromogranin A and wherein the endocrine cell subpopulation expresses Chromogranin A.

20. The cell population of claim 18, wherein the non-endocrine cell subpopulation is greater than the endocrine cell subpopulation.

21. The cell population of claim 18, wherein at least 30% of the encapsulated pancreatic progenitor cell population is the non-endocrine cell subpopulation.

22. The cell population of claim 18, wherein no more than 60% of the encapsulated pancreatic progenitor cell population is the endocrine cell subpopulation.

23. The cell population of claim 17, wherein the encapsulated pancreatic progenitor cell population is in a medium comprising an effective amount of growth factor selected from the group consisting of epidermal growth factor (EGF) or fibroblast growth factor.

24. The cell population of claim 23, wherein the EGF comprises a heregulin isoform.

25. The cell population of claim 24, wherein the heregulin isoform is selected from a group consisting of heregulin-1, heregulin-2, and heregulin-3 and heregulin-4.

26. The cell population of claim 23, wherein the effective amount of growth factor promotes differentiation of PDX1-positive cells to a non-endocrine cell subpopulation of the pancreatic progenitor cell population compared to the endocrine cell subpopulation of the pancreatic progenitor cell population.

27. The cell population of claim 17, wherein the encapsulated pancreatic progenitor cell population is transplanted in vivo.

28. The cell population of claim 17, wherein the transplanted pancreatic progenitor cell population matures in vivo to insulin producing cells.

29. The cell population of claim 17, wherein the encapsulated pancreatic progenitor cell population is in a semipermeable device comprising a semi-permeable membrane.

30. The cell population of claim 17, wherein the semi-permeable device comprises at least one cell encapsulating chamber.

31. The cell population of claim 17, wherein the at least one cell encapsulating chamber comprises at least one seal.

32. The cell population of claim 17, wherein the dedifferentiated human reprogrammed pluripotent stein cells are induced pluripotent stem cells.

33. The cell population of claim 17, wherein the 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.

34. The cell population of claim 17, further comprising an effective amount of heregulin wherein the heregulin promotes differentiation of PDX1-positive cells to the non-endocrine cell subpopulation to a greater extent than the endocrine cell subpopulation.

35. An encapsulated cell population derived from dedifferentiated human reprogrammed pluripotent stem cells wherein the 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.

36. A method of making an encapsulated pancreatic progenitor cell population comprising:

(a) exposing PDX1-positive cells to an effective amount of heregulin to make a pancreatic progenitor cell population; and

(b) encapsulating the pancreatic progenitor cell population thereby making an encapsulated pancreatic progenitor cell population.