Methods and compositions of growth control for cells encapsulated within bioartificial organs

• US 5,853,717 A
• Filed: 05/23/1995
• Issued: 12/29/1998
• Est. Priority Date: 07/20/1994
• Status: Expired due to Fees

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Cytotherapeutics, Inc.
• Inventors: Aebischer, Patrick, Shoichet, Molly S., Hammang, Joseph P., Doherty, Edward J., Gentile, Frank T., Holland, Laura M., Winn, Shelley R., Cain, Brian M., Schinstine, Malcolm
• Primary Examiner(s): Ketter, James
• Assistant Examiner(s): Yucel, Irem
• Application Number:
  US08/447,356
• Time in Patent Office: 1,316 Days
• Field of Search: 435/240, 435/243, 435/402, 435/395, 435/382, 435/372.3, 435/372.2, 435/382.2, 435/326, 424/93.21, 427/2.24
• US Class Current: 424/93.21
• 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. A method for controlling distribution of cells within a bioartificial organ comprising:

(a) providing a biocompatible, permselective jacket defining an internal volume;

(b) forming an inert scaffold within the internal volume defined by the jacket, wherein the inert scaffold is formed from a compound selected from the group consisting of poly(hydroxyethyl methacrylate) and poly(hydroxethyl methacrylate-co-methyl methacrylate); and

(c) loading cells within the internal volume defined by the jacket, wherein the inert scaffold provides a structure for adhering and distributing the cells within the bioartificial organ.

2. The method according to claim 1, wherein the inert scaffold is modified with a cell adhesion peptide.

4. The method according to claim 1 or 3 wherein the cells are primary cells or immortalized cell lines.

5. The method according to claim 1 or 3 wherein the cells are selected from the group consisting of baby hamster kidney cells and C₂ C₁₂ cells.

6. The method according to claim 1 or 3 wherein the cells are modified to secrete a biologically active molecule.

7. The method according to claim 6 wherein the cells secrete a biologically active molecule selected from the group consisting of hormones, cytokines, growth factors, trophic factors, angiogenesis factors, antibodies, blood coagulation factors, lymphokines, and enzymes.

3. A method for controlling distribution of cells within a bioartificial organ comprising:

(a) providing a biocompatible, permselective jacket defining an internal volume,

(b) growing cells on an inert scaffold comprising a non-woven polyester fabric, the inert scaffold providing a structure for adhering and distributing the cells within the bioartificial organ; and

(c) loading the inert scaffold with the cells within the internal volume defined by the jacket.

8. A bioartificial organ comprising:

(a) a biocompatible, permselective jacket defining an internal volume;

(b) a core of living cells encapsulated within the internal volume defined by the jacket; and

(c) an inert scaffold within the internal volume defined by the jacket, wherein the inert scaffold is formed from a compound selected from the group consisting of poly(hydroxyethyl methacrylate) and poly(hydroxyethyl methacrylate-co-methyl methacrylate), and provides a structure for adhering and distributing the cells.

9. The bioartificial organ according to claim 8 wherein the inert scaffold is modified with a cell adhesion peptide.

10. A bioartificial organ comprising:

(a) a biocompatible, permselective jacket defining an internal volume;

(b) a core of living cells encapsulated within the internal volume defined by the jacket, and

(c) an inert scaffold within the internal volume defined by the jacket, wherein the inert scaffold comprises a non-woven polyester fabric and provides a structure for adhering and distributing the cells within the bioartificial organ.

11. The bioartificial organ according to claim 8 or 10 wherein the cells are primary cells or immortalized cell lines.

12. The bioartificial organ according to claim 8 or 10 wherein the cells are selected from the group consisting of baby hamster kidney cells and C₂ C₁₂ cells.

13. The bioartificial organ according to claim 8 or 10 wherein the cells are modified to secrete a biologically active molecule.

14. The bioartificial organ according to claim 13 wherein the cells secrete a biologically active molecule selected from the group consisting of hormones, cytokines, growth factors, trophic factors, angiogenesis factors, antibodies, blood coagulation factors, lymphokines, and enzymes.