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

• US 5,840,576 A
• Filed: 05/23/1995
• Issued: 11/24/1998
• Est. Priority Date: 07/20/1994
• Status: Expired due to Term

• 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): Archutamurthy, Ponnathapura
• Application Number:
  US08/445,193
• Time in Patent Office: 1,281 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 27/383 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 suspending the cells in a hydrogel matrix within the bioartificial organ, the matrix being derivatized with a cell proliferation-inhibiting or cell differentiation-inducing peptide or peptide sequence wherein the hydrogel matrix is composed of agarose derivatized with a peptide sequence selected from the group consisting of an RGD-containing sequence, (ArgGlyAsp;

AA₂ -AA₄ of SEQ ID NO;

2), a YIGSR-containing sequence (TyrIleGlySerArg;

AA₅ -AA₉ of SEQ ID NO;

1) and an IKVAV-containing sequence (IleLysVaLAlaVal;

AA₁₁ -AA₁₅ of SEQ ID NO;

3).

2. The method according to claim 1, wherein the cells are grown on microcarriers suspended in the hydrogel matrix.

3. The method of claim 2 wherein the microcarrier is selected from the group consisting of dextran microcarriers, gelatin microcarriers and glass microcarriers.

4. The method of claim 2 wherein the microcarrier is coated with an effective amount of at least one extracellular matrix molecule.