Title:
INSULIN PRODUCING CELLS
Document Type and Number:
WIPO Patent Application WO2004061091
Kind Code:
A3
Abstract:
The present invention relates to a method for modifying liver cells such that they produce and store insulin. In addition, the invention relates to these modified cells and their use in the treatment of insulin-dependant diabetes. Accordingly the present invention provides a modified human hepatic cell characterised in that said cell is insulin-producing. In addition, the present invention provides a method for making an insulin-producing cell line comprising the steps of: (i.) isolating human hepatic progenitor cells; (ii.) introducing a construct for expressing Pdx 1 into said cells; and (iii.) selecting and isolating cells which express Pdx 1.
Inventors:
EFRAT SHIMON (IL)
Application Number:
PCT/GB2004/000005
Publication Date:
September 02, 2004
Filing Date:
January 05, 2004
Export Citation:
Assignee:
OXFORD BIOMEDICA LTD (GB)
EFRAT SHIMON (IL)
EFRAT SHIMON (IL)
International Classes:
A61P5/48; C12N5/071; A61K35/12; (IPC1-7): C12N5/08; A61P5/48; C12N5/10; C12N15/867
Domestic Patent References:
| WO2003078636A1 | 2003-09-25 |
Foreign References:
| EP1354942A1 | 2003-10-22 |
Other References:
FERBER S ET AL: "Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia.", NATURE MEDICINE, vol. 6, no. 5, May 2000 (2000-05-01), pages 568 - 572, XP002154420, ISSN: 1078-8956
YANG L ET AL: "In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 99, no. 12, 11 June 2002 (2002-06-11), pages 8078 - 8083, XP002961837, ISSN: 0027-8424
HORB M E ET AL: "Experimental conversion of liver to pancreas.", CURRENT BIOLOGY, vol. 13, no. 2, 21 January 2003 (2003-01-21), pages 105 - 115, XP009013033, ISSN: 0960-9822
ZALZMAN M ET AL: "Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 100, no. 12, 10 June 2003 (2003-06-10), pages 7253 - 7258, XP002284492, ISSN: 0027-8424
NALDINI L ET AL: "Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 93, no. 21, 15 October 1996 (1996-10-15), pages 11382 - 11388, XP002114690, ISSN: 0027-8424
ANNICOTTE J-S ET AL: "Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development.", MOLECULAR AND CELLULAR BIOLOGY, vol. 23, no. 19, October 2003 (2003-10-01), pages 6713 - 6724, XP002284495, ISSN: 0270-7306
KOJIMA H ET AL: "Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin.", DIABETES., vol. 51, no. 5, May 2002 (2002-05-01), pages 1398 - 1408, XP002284493, ISSN: 0012-1797
MCKINNON C M & DOCHERTY K: "Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function.", DIABETOLOGIA, vol. 44, no. 10, October 2001 (2001-10-01), pages 1203 - 1214, XP001176889, ISSN: 0012-186X
MALHI H ET AL: "Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes.", JOURNAL OF CELL SCIENCE, vol. 115, no. Pt 13, 1 July 2002 (2002-07-01), pages 2679 - 2688, XP002284494, ISSN: 0021-9533
DUFAYET DE LA TOUR D ET AL: "Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo.", MOLECULAR ENDOCRINOLOGY, vol. 15, no. 3, March 2001 (2001-03-01), pages 476 - 483, XP002962265, ISSN: 0888-8809
YANG L ET AL: "In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 99, no. 12, 11 June 2002 (2002-06-11), pages 8078 - 8083, XP002961837, ISSN: 0027-8424
HORB M E ET AL: "Experimental conversion of liver to pancreas.", CURRENT BIOLOGY, vol. 13, no. 2, 21 January 2003 (2003-01-21), pages 105 - 115, XP009013033, ISSN: 0960-9822
ZALZMAN M ET AL: "Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 100, no. 12, 10 June 2003 (2003-06-10), pages 7253 - 7258, XP002284492, ISSN: 0027-8424
NALDINI L ET AL: "Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 93, no. 21, 15 October 1996 (1996-10-15), pages 11382 - 11388, XP002114690, ISSN: 0027-8424
ANNICOTTE J-S ET AL: "Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development.", MOLECULAR AND CELLULAR BIOLOGY, vol. 23, no. 19, October 2003 (2003-10-01), pages 6713 - 6724, XP002284495, ISSN: 0270-7306
KOJIMA H ET AL: "Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin.", DIABETES., vol. 51, no. 5, May 2002 (2002-05-01), pages 1398 - 1408, XP002284493, ISSN: 0012-1797
MCKINNON C M & DOCHERTY K: "Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function.", DIABETOLOGIA, vol. 44, no. 10, October 2001 (2001-10-01), pages 1203 - 1214, XP001176889, ISSN: 0012-186X
MALHI H ET AL: "Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes.", JOURNAL OF CELL SCIENCE, vol. 115, no. Pt 13, 1 July 2002 (2002-07-01), pages 2679 - 2688, XP002284494, ISSN: 0021-9533
DUFAYET DE LA TOUR D ET AL: "Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo.", MOLECULAR ENDOCRINOLOGY, vol. 15, no. 3, March 2001 (2001-03-01), pages 476 - 483, XP002962265, ISSN: 0888-8809
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