Organogenesis, Inc.

Other

Paul A DiMilla

Maury D Cosman

Susan J Sullivan

Paul G Gregory

Lisa Romito

Chris Gemmeti

Rachel Halych

Kevin Odlum

Mehmet Toner

Martin L Yarmush

Ulysses J Balis

Arno W Tilles

The invention features modular chambers for culturing cells in which the volume of a chamber can be adjusted without compromising the seal or sterility of the chamber. The invention is based on the principle that the volume of a chamber formed between two plates sandwiching a compressible gasket and a substantially incompressible stop can be adjusted using a gasket that forms a fluid-tight seal between the plates at a plurality of levels of compression. The invention enables the culture of cells between substantially parallel and rigid plates in which a relatively large volume can be used to seed the cells and the holdup volume reduced for perfusion without opening or otherwise disassembling the system to compromise its liquidtightness and sterility. The new closed, modular and scalable cell-culturing chamber can be thus perfused and used to culture cells (e.g., hepatocytes) with high levels of cell function in organ (e.g., liver) assist systems, for production of cells, for production of cell-derived products, such as proteins or viruses, or for systems to treat biological liquids to remove toxins, such as ammonia, add cell-synthesized products, or both.

Chamber with adjustable volume for cell culture and organ assist

The invention features a liver cell culture comprising hepatocytes that have increased detoxification enzyme activity when isolated from a liver of a donor that had been administered at least one induction agent prior isolation of hepatocyte cells. The induced hepatocytes are used in a bioreactor and cultured to produce hepatocyte cell products or metabolize toxins added to the culture. The bioreactor is, or is an integral part of, a liver assist device used to treat a patient in need of liver assist.

In vivo induction for enhanced function of isolated hepatocytes

The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.

Cell culture systems and methods for organ assist devices

Vivo induction for enhanced function of isolated hepatocytes

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Dover, MA, United States of America

Paul A DiMilla