ARNO WILLIAM TILLES, MD
Osteopathic Medicine at Rogers St, Cambridge, MA

6465252, Oct 15, 2002

Jun 21, 2000

09/599891

Mehmet Toner - Wellesley MA
Arno W. Tilles - Cambridge MA
Ulysses J. Balis - Peabody MA
Martin L. Yarmush - Newton MA
Maury D. Cosman - Woburn MA
Paul A. Dimilla - Dover MA

The General Hospital Corporation - Boston MA
Organogenesis Inc. - Canton MA

C12N 500

435401, 4352841, 4352971, 4352972, 435402, 435395, 435399

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.

6562616, May 13, 2003

Jun 21, 2000

09/599297

Mehmet Toner - Wellesley MA
Martin L. Yarmush - Newton MA
Ulysses J. Balis - Peabody MA
Arno W. Tilles - Cambridge MA

The General Hospital Corporation - Boston MA

C12M 304

4352931, 4352932, 4352972, 435370, 435395, 604 504

The invention relates to new flow-through cell culturing devices that include plates arranged in parallel and spaced to control the flow patterns and velocity of liquid medium flowing between the plates. The devices can also include gas-permeable, liquid impermeable membranes arranged between the plates. The devices can be used to culture cells, such as hepatocytes, at high levels of mass transport of nutrients, oxygen, and waste products, yet low levels of shear stress for extended periods of time and with high levels of cell function, e. g. , in organ assist systems. The invention also includes new culturing plates for use in the devices, and methods of manufacturing these plates.

6759245, Jul 6, 2004

Jun 21, 2000

09/599891

Mehmet Toner - Wellesley MA
Arno W. Tilles - Cambridge MA
Ulysses J. Balis - Peabody MA
Martin L. Yarmush - Newton MA
Maury D. Cosman - Woburn MA
Paul A. Dimilla - Dover MA

The General Hospital Corporation - Boston MA
Organogenesis Inc. - Canton MA

C12N 500

435401, 4352841, 4352971, 4352972, 435402, 435395, 435399

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.

2010014, Jun 10, 2010

Dec 10, 2009

12/634983

Martin L. Yarmush - Newton MA, US
Cheul H. Cho - Whippany NJ, US
Arno W. Tilles - Cambridge MA, US

THE GENERAL HOSPITAL CORPORATION - Boston MA

A61K 35/407, C12N 5/074, A61P 1/16

424 937, 435377

One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. Although embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. The present invention provides for a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. In one embodiment, mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiate and proliferate into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17 and AFP, and could further differentiate into hepatocyte-like cells that demonstrate hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.

2003001, Jan 23, 2003

Jul 15, 2002

10/196653

Mehmet Toner - Wellesley MA, US
Arno Tilles - Cambridge MA, US
Ulysses Balis - Peabody MA, US
Martin Yarmush - Newton MA, US
Maury Cosman - Woburn MA, US
Paul Dimilla - Dover MA, US

The General Hospital Corporation, a Massachusetts corporation

A61K045/00, C12N005/08

424/093700, 435/370000

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.