Stem cells and pancreatic cells useful for the treatment of insulin-dependent diabetes mellitus

• US 9,968,639 B2
• Filed: 06/24/2013
• Issued: 05/15/2018
• Est. Priority Date: 06/26/2012
• Status: Active Grant

• Current Assignee: Seraxis, Inc. (Seraxis Pte Ltd.)
• Original Assignee: Seraxis, Inc. (Seraxis Pte Ltd.)
• Inventors: Rust, William L.
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US13/925,248
• Publication Number:
  US 20130344594A1
• Time in Patent Office: 1,786 Days
• Field of Search: None
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/05 Inorganic components
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/30 Organic components metal chelators C12N2500/10; calcitonin C12N2500/14; transferrin C12N2500/24
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/42 Organic phosphate, e.g. beta glycerophosphate
• 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 2501/15 Transforming growth factor beta (TGF-β)
• 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 2501/60 Transcription factors
• CPC Class Codes: C12N 2502/1329 Cardiomyocytes
• CPC Class Codes: C12N 2506/22 from pancreatic cells
• CPC Class Codes: C12N 2506/45 from artificially induced pluripotent stem cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells

Abstract

Fresh human pancreas tissue can be used as a source of cells when to identify and select a non-stem cell population that is predisposed to be a source for surrogate pancreatic cells that can be used in treating insulin-dependent diabetes. The progenitors of these surrogate pancreatic cells have no reprogramming genes integrated into their genomes, differentiate to the pancreatic lineage pursuant to a protocol that employs only defined reagents, and are substantially unable to differentiate to the mesodermal lineage.

Claims

1. A composition comprising non-pluripotent progenitors of surrogate pancreatic cells, wherein the non-pluripotent progenitors comprise a varied population of native pancreatic cells that were harvested from a subject'"'"'s pancreas, wherein the non-pluripotent progenitors have been cultured in only defined, non-animal origin reagents for fewer than five population doublings, and wherein the non-pluripotent progenitors are unable to differentiate into the mesodermal lineage, but can differentiate into surrogate pancreatic cells that are suitable for treating insulin-dependent diabetes.

2. The composition of claim 1, wherein the progenitors have the ability to proliferate in culture conditions comprises defined, non-animal-origin components.

3. The composition of claim 1, wherein the progenitors have no reprogramming genes integrated into their genomes.

4. The composition of claim 1, wherein the progenitors have the ability to respond to a minimal differentiation protocol by differentiating into a substantially pure population of pancreatic cells.

5. The composition of claim 4, wherein the substantially pure population of pancreatic cells comprises at least about 80% of cells that express genes characteristic of pancreatic endocrine progenitors and that can mature into hormone-producing cells of the islets of Langerhans.

6. The composition of claim 4, wherein the substantially pure population of pancreatic cells comprises at least about 90% of cells that express genes characteristic of pancreatic endocrine progenitors and that can mature into hormone-producing cells of the islets of Langerhans.

7. The composition of claim 1, wherein more than about 90% of cells comprising the composition express the markers Pdx1, Nkx6.1, and NeuroD1.

8. A composition comprising non-pluripotent progenitors of surrogate pancreatic cells, wherein the non-pluripotent progenitors have the ability to survive a differentiation protocol such that a large population of pancreatic cells can be efficiently produced, wherein the differentiation protocol comprises defined, non-animal-origin components, and wherein the non-pluripotent progenitors are unable to differentiate into the mesodermal lineage, but can be differentiated into surrogate pancreatic cells that are suitable for treating insulin-dependent diabetes.

9. The composition of claim 8, wherein the differentiation protocol does not comprise contacting the progenitors with a wnt family member.

10. The composition of claim 8, wherein the differentiation protocol comprises a first combination of components that drive differentiation to an endodermal lineage, whereby endodermal cells are obtained, and then exposing said endodermal cells to a combination of components that drive differentiation to a pancreatic endocrine lineage.

11. The composition of claim 8, wherein the progenitors have no reprogramming genes integrated into their genomes.

12. The composition of claim 8, wherein more than about 90% of cells comprising the composition express the markers Pdx1, Nkx6.1, and NeuroD1.