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专利名称：Controlling proliferation of cells before and
after encapsulation in a bioartificial organ bygene transformation
发明人：Malcolm Schinstine,Molly S. Shoichet,Frank
T. Gentile,Joseph P. Hammang,Laura M.Holland,Brian M. Cain,Edward J.
Doherty,Shelley R. Winn,Patrick Aebischer
申请号：US08/432698申请日：19950509公开号：US05843431A公开日：19981201
摘要：Methods and compositions are provided for controlling cell distribution withinan implantable bioartificial organ by exposing the cells to a treatment that inhibits cellproliferation, promotes cell differentiation, or affects cell attachment to a growthsurface within the bioartificial organ. Such treatments include (1) genetically manipulatingcells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulatingcompound or a differentiation-inhibiting compound; exposing the cells to irradiation, and(3) modifying a growth surface of the bioartificial organ with extracellular matrixmolecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or acombination thereof. These treatments may be used in combination. Cells can be
transformed with a proliferation-promoting gene such as the oncogene, SV40, linked to aregulatable 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 orafter insertion of the cells in the bioartificial organ to inhibit expression of the gene toreduce or stop cell proliferation in vivo. The promoter can be reactivated in vivo to againexpress the gene to result in further cell proliferation. The gene may be a proliferation-suppressing gene such as p53 gene or RB gene, or a differentiation-inducing gene such ashigh mobility group chromosomal protein 14. Inhibiting gene expression in vitro causescell proliferation, and inducing gene expression reduces or stops cell proliferation in vivo.
申请人：CYTOTHERAPEUTICS, INC.
代理人：Ivor R.Mintz, Levin Elrifi
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