Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation

US5843431A · kind A · utility

Assignee

• Cytotherapeutics, Inc. · US

Inventors

• Malcolm Schinstine · Lehighton, US
• Molly S. Shoichet · Toronto, CA
• Frank T. Gentile · East Greenwich, US
• Joseph P. Hammang · Barrington, US
• Laura M. Holland · Ambler, US
• Brian M. Cain · Everett, US
• Edward J. Doherty · Halifax, US
• Shelley R. Winn · Providence, US
• Patrick Aebischer · Lutry, CH

Key dates

• Filing date: May 9, 1995
• Grant date: Dec 1, 1998
• Expiry date: May 9, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2533/74
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Methods and compositions are provided for controlling cell distribution within an implantable 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 bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. Cells can be transformed with a proliferation-promoting gene such as the oncogene, SV40, linked to a regulatable promoter such as the Mx1 promoter, the promotor is activated in vitro to express the gene to result in cell proliferation, and the promotor is inactivated before or after insertion of the cells in the bioartificial organ to inhibit ex…