Methods of reprogramming cells

• US 10,221,393 B2
• Filed: 06/19/2017
• Issued: 03/05/2019
• Est. Priority Date: 08/22/2008
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Melton, Douglas A., Zhou, Qiao
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Nguyen, Nghi V
• Application Number:
  US15/627,381
• Publication Number:
  US 20170355962A1
• Time in Patent Office: 624 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2501/60 Transcription factors
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

The present invention provides methods of reprogramming cells, for example, directly reprogramming a somatic cell of a first cell type into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for reprogramming a cell of an endoderm origin to a cell having pancreatic β-cell characteristics. The present invention also relates to an isolated population comprising reprogrammed cells, compositions and their use in the treatment of diabetes mellitus. In particular, the present invention relates to reprogramming a cell of an endoderm origin to a cell having pancreatic β-cell characteristics by increasing the protein expression of at least one transcription factor selected from Pdx1, Ngn3 or MafA in the cell of endoderm origin to reprogram the cell of an endoderm cell to a cell which exhibits at least one or at least two characteristics of an endogenous pancreatic β-cell.

Claims

1. A method for the treatment of a subject with diabetes, the method comprising administering a composition comprising an isolated population of pancreatic β

-like cells obtained from a population of mature exocrine cells by a process comprising increasing the protein expression of Pdx-1, Ngn3, and MafA, or a functional fragment thereof, in the mature exocrine cells, wherein the pancreatic β

-like cells do not express pancreatic hormones other than insulin.

2. The method of claim 1, wherein the pancreatic β

-like cells are produced from mature exocrine cells obtained from the same subject as the composition is administered to.

3. The method of claim 1, wherein the subject has, or has an increased risk of developing, diabetes.

4. The method of claim 1, wherein the diabetes is selected from the group consisting of:

Type I diabetes, Type II diabetes and pre-diabetes.

5. The method of claim 1, wherein the subject has, or has an increased risk of developing, a metabolic disorder.