University of Minnesota

Katholieke Universiteit Leuven

Other

Bsi Corporation

Wei-Shou Hu

Catherine M Verfaillie

Kartik Subramanian

Frank B Cerra

Matthew T Scholz

Yonsil Park

Russell A Shatford

Scott Lyle Nyberg

David L Clapper

David H Sherman

Gargi Seth

Anna F Europa

Stephane Goetghebeur

Li-Hong Malmberg

M Verfaillie Catherine

The invention is directed to compositions of cell aggregates and methods for making and using the cell aggregates where the aggregates comprise cells that are not embryonic stem cells but can differentiate into cell types of at least two of ectodermal, undo dermal, and mesodermal embryonic germ layers, e.g., stem cells.

Stem cell aggregates and methods for making and using

The invention is directed to compositions of cell aggregates and methods for making and using the cell aggregates where the aggregates comprise cells that are not embryonic stem cells but can differentiate into cell types of at least two of ectodermal, endodermal, and mesodermal embryonic germ layers, e.g., stem cells.

Non-static suspension culture of cell aggregates

Gene complementation is used to restore cholesterol independence in NS lineage murine myeloma cells, such as NS0 and NS 1, yielding a selectable system for recombinant production of polynucleotides and polypeptides.

Restoration of cholesterol independence and its use as a selectable marker in NS0 cell culture

Process for the continuous culture of cells

Methods of maintaining animal cells for product production, for supporting hepatocyte function and viability to treat a patient suffering from hepatic failure and for preserving tissue-specific function of mammalian cells are carried out with a bioreactor containing a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible contracted three-dimensional gel matrix entraps animal cells or genetic modifications thereof, and a liquid phase contains a concentrated solution of the cell product. The bioreactor uses only two chambers to achieve three distinct zones within the bioreactor. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports. Communication between the two fluid paths is across the permeable medium--the hollow fiber material. To prepare a bioartificial liver, hepatocytes are inoculated into the hollow fibers in a solution which quickly forms a highly porous gel. The gel subsequently contracts, leaving an open channel within the hollow fiber adjacent to the gel core entrapped hepatocytes. This channel can be perfused with nutrient media for hepatocytes. The channel can also serve as a waste stream to remove toxins that the hepatocytes have modified to a water soluble form.

Maintaining cells for an extended time by entrapment in a contracted

A bioreactor apparatus comprising two chambers, a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible three-dimensional matrix entraps animal cells or genetic modifications thereof. Due to the presence of this biocompatible matrix, the cell chamber generally has a gel phase, i.e., the biocompatible matrix and cells, and a liquid phase containing a concentrated solution of the cell product to be harvested. Thus, the bioreactor of this invention uses only two chambers to achieve three distinct zones within the apparatus. A bioartificial liver is based on a bioreactor of the type having two fluid paths separated by a permeable medium. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports. Communication between the two fluid paths is across the permeable medium--the hollow fiber material. Hepatocytes are inoculated into the hollow fibers in a solution which quickly forms a highly porous gel. The gel subsequently contracts, leaving an open channel within the hollow fiber adjacent to the gel core entrapped hepatocytes. This channel can be perfused with nutrient media for hepatocytes. The channel can also serve as a waste stream to remove toxins that the hepatocytes have modified to a water soluble form.

Bioreactor device with application as a bioartificial liver

A filter device containing cell masses and single cells is described. The device contains porous hollow fibers and hepatocytes entrapped within a contracted gel matrix.

Filter device

A combination of a cell adhesion factor and a positively-charged molecule are bound to the surface of a cell culture support of a bioreactor to improve cell attachment and stabilize cell growth. The positively charged molecule is preferably polylysine, chitosan, poly(ethyleneimine) or acrylics polymerized from acrylamide or methacrylamide and incorporating positively-charged groups in the form of primary, secondary or tertiary amines, or quaternary salts. The cell adhesion factor is preferably fibronectin, laminin, collagen, vitronectin or tenascin, or fragments or analogs having a cell binding domain thereof. The positively-charged molecule and the cell adhesion factor can be covalently bound to the supporting surface. In another embodiment, the positively-charged molecule and the cell adhesion factor are covalently bound to one another and either the positively-charged molecule or the cell adhesion factor is covalently bound to the supporting surface. Also, the positively-charged molecule or the cell adhesion factor or both cam be provided in the form of a stable coating non-covalently bound around the surface of the support. The cell culture support may be in the form of a microcarrier and can be made of polystyrene or polypropylene

Cell culture support containing a cell adhesion factor and a

Targeted gene insertion methodology can increase the production of an antimicrobial metabolite and comprises the steps of:

Method for increasing production of microbial metabolites by genetic

A method of inducing aggregate formation of animal cells is carried out by forming a nutrient medium suspension of animal cells and introducing itno the suspension microspheres of a derivatized diameter of not more than about 60 .mu.m, when measured in a suitable buffer saline or cell culture media.

Growing community of inventors

Falcon Heights, MN, United States of America

Wei-Shou Hu