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

• US 5,935,849 A
• Filed: 07/20/1994
• Issued: 08/10/1999
• 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: Shoichet, Molly S., Holland, Laura M., Schinstine, Malcolm, Aebischer, Patrick, Hammang, Joseph P., Doherty, Edward J., Gentile, Frank T., Winn, Shelley R., Cain, Brian M.
• Primary Examiner(s): ACHUTAMURTHY, PONNATHAPURA N
• Application Number:
  US08/279,773
• Time in Patent Office: 1,847 Days
• Field of Search: 435/240.2, 435/240.22, 435/240.23, 435/240.242, 435/240.243, 435/325, 435/375, 435/377, 435/400
• US Class Current: 435/325
• 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 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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: 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 thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• 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 exposing at least one growth surface within the bioartificial organ to a treatment that inhibits cell proliferation or promotes cell differentiation, wherein the treatment comprises coating the growth surface with an effective amount of at least one extracellular matrix molecule, the extracellular matrix molecule coating formed by culturing extracellular matrix molecule-forming cells on the growth surface and then lysing the cells extracellular matrix molecule-forming cells to produce a coating of at least one acellular extracellular matrix molecule on the growth surface.

2. The method according to claim 1, wherein the growth surface coated with the extracellular matrix molecule comprises an inner luminal surface of the bioartificial organ.

3. The method according to claim 1, wherein the growth surface coated with the extracellular matrix molecule comprises microcarriers encapsulated within the bioartificial organ.

4. The method according to claim 1, wherein the treatment further comprises adding growth factors or chemical compounds to the extracellular matrix molecules.

5. A bioartificial organ comprising:

(a) a biocompatible jacket;

(b) a core of living cells; and

(c) at least one growth factor within the bioartificial organ that is exposed to a treatment that inhibits cell proliferation or promotes cell differentiation comprising coating the growth surface with at least one extracellular matrix molecule,

wherein the treatment comprises coating the growth surface with an effective amount of at least one extracellular matrix molecule, the extracellular matrix molecule coating formed by culturing extracellular matrix molecule-forming cells on the growth surface and then lysing the extracellular matrix molecule-forming cells to produce a coating of at least one acellular extracellular matrix molecule on the growth surface.

6. The bioartificial organ of claim 5, wherein the growth surface is selected from the group consisting of a luminal surface of the bioartificial organ, an inner scaffold surface, an inner support surface, an internal membrane, and a surface of a microcarrier encapsulated within the bioartificial organ.

7. The bioartificial organ of claim 5, wherein growth factors or chemical compounds are added to the extracellular matrix molecule.