Mx-1 conditionally immortalized cells

• US 6,392,118 B1
• Filed: 05/23/1995
• Issued: 05/21/2002
• Est. Priority Date: 07/20/1994
• Status: Expired due to Fees

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Neurotech S.A. (LivaNova Plc)
• Inventors: Messing, Albee, Hammang, Joseph P.
• Primary Examiner(s): NGUYEN, DAVE TRONG
• Application Number:
  US08/447,997
• Time in Patent Office: 2,555 Days
• Field of Search: 435/325, 435/320.1, 435/455, 536/23.72, 536/23.1, 536/24.1, 536/23.51, 536/23.52, 536/23.2, 536/23.5, 935/6, 935/9, 935/11, 935/13, 935/14, 935/15, 935/22, 935/32, 935/66, 935/70, 935/71, 800/2, 800/DIG.1, 800/18
• US Class Current: 800/14
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C08L 83/12 containing polyether sequences
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2510/04 Immortalised cells
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

Claims

1. An isolated cell transformed with a recombinant DNA molecule comprising:

a) a proliferation-promoting gene for inducing cell division when expressed,

b) an Mx-1 promoter operably linked to the proliferation-promoting gene,

wherein said isolated cell is induced to proliferate by exposure to an amount of interferon sufficient to result in expression of the proliferation-promoting gene.

2. The cell of claim 1 wherein the proliferation-promoting gene is SV 40 large T antigen.

3. The cell of claim 1 wherein the cell secretes a biologically active molecule.

4. The cell of claim 3 wherein the cell is genetically transformed with an expression vector containing a gene that encodes the biologically active molecule.

5. The cell of claims 3 or 4 wherein the biologically active molecule is selected from the group consisting of neurotransmitters, hormones, cytokines, growth factors, trophic factors, lymphokines, angiogenesis factors, antibodies, blood coagulation factors, and enzymes.

6. The cell of claim 1 wherein the cell is obtained from a neural stem cell.

7. A transgenic mouse, whose genome comprises a recombinant DNA molecule comprising:

a) a proliferation-promoting gene for inducing gene expression when expressed,

b) an Mx-1 promoter operably linked to the proliferation-promoting gene,

wherein said transgenic mouse contains cells which are induced to proliferate by exposure to an amount of interferon sufficient to result in expression of the proliferation-promoting gene.

8. The transgenic mouse of claim 7, wherein the proliferation-promoting gene is SV-40 large T antigen.

9. Progeny of the transgenic mouse of claim 7.

10. A cell isolated from the transgenic mouse of either claim 7 or 9.

11. The cell of claim 10, wherein the cell is a neural stem cell.

12. A method of generating a conditionally immortalized cell, comprising the steps of:

a) transforming an isolated cell with a recombinant DNA molecule comprising a proliferation-promoting gene for inducing cell division when expressed and an Mx-1 promoter operably linked to the proliferation-promoting gene, such that said transformed cell is induced to proliferate by exposure to an amount of interferon sufficient to result in expression of the proliferation-promoting gene;

b) and culturing said transformed isolated cell.