Method of pre-inducing a state of immune tolerance before organ transplantation

• US 6,923,959 B2
• Filed: 05/02/2002
• Issued: 08/02/2005
• Est. Priority Date: 12/06/1999
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Faustman, Denise L., Thomas, Melissa K., Habener, Joel F., Vallejo, Mario, Abraham, Elizabeth J., Zulewski, Henryk
• Primary Examiner(s): Kemmerer, Elizabeth C.
• Assistant Examiner(s): Bunner, Bridget E.
• Application Number:
  US10/136,891
• Publication Number:
  US 20030031657A1
• Time in Patent Office: 1,188 Days
• Field of Search: 435/4, 435/325, 435/1.1, 424/93.1, 424/93.7, 424/520
• US Class Current: 424/93.7
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/34 Sugars
• 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 2501/335 Glucagon; Glucagon-like peptide [GLP]; Exendin
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: C12N 5/0678 Stem cells; Progenitor cells; Precursor cells

Abstract

Methods and compositions are described for the treatment of type I insulin-dependent diabetes mellitus and other conditions using newly identified stem cells that are capable of differentiation into a variety of pancreatic islet cells, including insulin-producing beta cells, as well as hepatocytes. Nestin has been identified as a molecular marker for pancreatic stem cells, while cytokeratin-19 serves as a marker for a distinct class of islet ductal cells. Methods are described whereby nestin-positive stem cells can be isolated from pancreatic islets and cultured to obtain further stem cells or pseudo-islet like structures. Methods for ex vivo differentiation of the pancreatic stem cells are disclosed. Methods are described whereby pancreatic stem cells can be isolated, expanded, and transplanted into a patient in need thereof, either allogeneically, isogeneically or xenogenically, to provide replacement for lost or damaged insulin-secreting cells or other cells.

Claims

1. A method of transplanting an organ in a mammal without the administration of immunosuppressive drugs, comprising the steps of:

(a) isolating nestin-positive pancreatic stem cells from a pancreatic islet of a mammalian donor;

(b) transplanting said nestin-positive pancreatic stem cells into a mammalian transplant recipient, wherein said transplanting induces a state of immune tolerance in the recipient toward the donor'"'"'s stem cells; and

(c) transplanting an organ from said donor to said recipient, wherein said organ is trasplanted without the administration of immunosuppressive drugs.

2. A method of pre-inducing a state of immune tolerance prior to organ transplantation, comprising the steps of:

(a) isolating nestin-positive pancreatic stem cells from a pancreatic islet of a mammalian donor; and

(b) transplanting said nestin-positive pancreatic stem cells into a mammalian transplant recepient, wherein said transplanting induces a state of immune tolerance in the recipient toward the donor'"'"'s stem cells prior to organ transplantation.