Compositions and methods for treating type 1 and type 2 diabetes and related disorders

Patent metadata

Field	Value
Publication number	US-9546379-B2
Application number	US-201514793391-A
Country	US
Kind code	B2
Filing date	Jul 7, 2015
Priority date	Mar 27, 2014
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

First claim

What is claimed is:

1. An in vitro method for differentiating a pancreatic β-cell progenitor into a mature β-cell comprising the step of:
contacting a pancreatic β-cell progenitor cell which expresses PDX1 and insulin with a viral vector encoding estrogen-related receptor γ (ERRγ) in an amount sufficient to overexpress ERRγ in the cell;
wherein said contacting differentiates the pancreatic β-cell progenitor cell into a mature β-cell which is capable of glucose-stimulated insulin secretion.

2. The method of claim 1 , wherein the pancreatic β-cell progenitor expresses one or more β cell transcription factors selected from the group consisting of Nkx2.2, NeuroD1, Foxa2, Pax6, HNF4a MafA and Nkx6-1.

3. The method of claim 1 , wherein the pancreatic β-cell progenitor expresses one or more β-cell markers selected from glucagon or somatostatin.

4. The method of claim 1 , wherein the mature pancreatic β-cell expresses one or more mRNA selected from the group consisting of Mafa, Pax6, NeuroD, GCK, CHGA, VAMP2, PC1/3, Glut2, Nkx6.1, GCG, SST, and U36B4.

Assignees

• Salk Inst For Biological Studi

Inventors

• Evans Ronald M
• Yoshihara Eiji
• Downes Michael R
• Yu Ruth T
• Atkins Annette R

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N15/85 Primary

  for animal cells · CPC title

• A61K35/35

  Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39) · CPC title

• C12N2710/10043

  viral genome or elements thereof as genetic vector · CPC title