Method of differentiating mammalian progenitor cells into insulin producing pancreatic islet cells

• US 9,605,244 B2
• Filed: 10/31/2014
• Issued: 03/28/2017
• Est. Priority Date: 05/22/2008
• Status: Active Grant

• Current Assignee: Vesta Therapeutics, Inc.
• Original Assignee: Vesta Therapeutics, Inc.
• Inventors: Ruiz, Joseph Charles, Hoynowski, Steven Michael
• Primary Examiner(s): LI, QIAN JANICE
• Application Number:
  US14/530,251
• Publication Number:
  US 20150056647A1
• Time in Patent Office: 879 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2500/30 Organic components metal chelators C12N2500/10; calcitonin C12N2500/14; transferrin C12N2500/24
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2500/90 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 2501/065 Modulators of histone acetylation
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 2506/14 from hepatocytes
• CPC Class Codes: C12N 2509/00 Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 5/067 Hepatocytes
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: G01N 33/5014 for testing toxicity
• CPC Class Codes: G01N 33/5038 involving detection of metabolites per se
• CPC Class Codes: G01N 33/507 Pancreatic cells

Abstract

The invention relates to methods for differentiating progenitor cells into insulin producing pancreatic islet cells and compositions and methods for using such cells.

Claims

1. A method for differentiating progenitor cells into insulin-producing pancreatic cells, comprising:

(a) incubating the progenitor cells in serum-free pre-induction media comprising a histone deacetylase inhibitor (HDACI); and

, subsequently,

(b) incubating the progenitor cell in induction media comprising knock-out replacement serum;

for a time sufficient to differentiate the progenitor cells into insulin producing pancreatic cells

wherein the progenitor cells are selected from the group consisting of hepatic stem cells, hepatoblasts, or hepatic committed progenitors.

2. The method according to claim 1 in which the progenitor cells are human progenitor cells.

3. The method according to claim 1 in which the progenitor cells are hepatic stem cells.

4. The method according to claim 1 in which the induction media comprises about 2% knock-out replacement serum.

5. The method according to claim 1 in which the HDACI is sodium butyrate, phenyl butyrate, retinoic acid, valproic acid, APHA Compound 8, Apicidin, (−

) Depudecin, Scriptaid, Sirtinol, and Trichostatin.