Abstract: The present invention relates to a method for promoting blood vessel formation in tissues and organs. In particular, the method relates to implantation or attachment of an engineered three-dimensional stromal tissue to promote endothelialization and angiogenesis in the heart and related tissues. The three-dimensional stromal tissue of the present invention may be used in a variety of applications including, but not limited to, promoting repair of and regeneration of damaged cardiac muscle, promoting vascularization and healing during cardiac surgery, promoting blood vessel formation at anastomosis sites, and promoting vascularization and repair of damaged skeletal muscle, smooth muscle or connective tissue.

Abstract: The present invention is directed to a container and method for shipping and storing frozen products. In particular, the present invention is directed to an insulated container for shipping and storing frozen tissue samples for an extended period of time, for example at least 72 hours. An exemplary embodiment of the container of the present invention includes a body having an open end and a product chamber lined with vacuum insulated panels, a spring assembly inside of the product chamber for supporting a lower cooling block and a stack of tissue packages (e.g. engineered tissue samples), and a lid assembly including one or more upper cooling blocks suspended therefrom. When the lid assembly is secured on the body of the container, the tissue packages are held in place between the upper and lower cooling blocks by the force of the spring assembly. The body of the container is dimensioned so that it may fit within an outer cardboard carton if desired for shipping.

Abstract: Novel products comprising conditioned cell culture medium compositions and methods of use are described. The conditioned cell medium compositions of the invention may be comprised of any known defined or undefined medium and may be conditioned using any eukaryotic cell type. The medium may be conditioned by stromal cells, parenchymal cells, mesenchymal stem cells, liver reserve cells, neural stem cells, pancreatic stem cells and/or embryonic stem cells. Additionally, the cells may be genetically modified. A three-dimensional tissue construct is preferred. Once the cell medium of the invention is conditioned, it may be used in any state. Physical embodiments of the conditioned medium include, but are not limited to, liquid or solid, frozen, lyophilized or dried into a powder.

Abstract: The present invention discloses compositions containing natural human extracellular matrices and methods for the use thereof. More particularly, the present invention provides compositions and methods for the repair of skin defects using natural human extracellular matrix by injection.

Abstract: The present invention discloses compositions containing natural human extracellular matrices and methods for the use thereof. More particularly, the present invention provides compositions and methods for the repair of skin defects using natural human extracellular matrix by injection.

Abstract: The invention relates to cells or tissues having an increased amount of regulatory proteins, including cytokines, growth factors, angiogenic factors and/or stress proteins, and methods of producing and using those cells or tissues. The invention is based on the discovery that the production of regulatory proteins is induced in cells or tissue constructs following cryopreservation and subsequent thawing of the cells or constructs. The compositions and methods of this invention are useful for the treatment of wound healing and the repair and/or regeneration of other tissue defects including those of skin, cartilage, bone, and vascular tissue as well as for enhancing the culture and/or differentiation of cells and tissues in vitro.

Abstract: The present invention discloses compositions containing natural human extracellular matrices and methods for the use thereof. More particularly, the present invention provides compositions and methods for the repair of skin defects using natural human extracellular matrix by injection.

Abstract: A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media; allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.

Abstract: A stromal cell-based three-dimensional cell culture system is provided which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells along with connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. Living stromal tissue so formed provides support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue.

Abstract: An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing three-dimensional tissue constructs is disclosed. The apparatus includes a fluid reservoir, a pump, at least one treatment chamber, and a means for controlling media flow characteristics around a tissue construct disposed within the treatment chamber, and for controlling movement of the construct itself, so as to simulate a variety of physiologic conditions. One exemplary embodiment of the invention includes a means for applying an axial stress to the construct. Applying an axial stress to the construct during seeding and culturing results in a tissue-engineered construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of native vessels with normal physiologic function.

Abstract: An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing cartilage constructs is disclosed. The apparatus generally includes a treatment chamber and a means for varying the fluid flow and pressure within the treatment chamber during seeding and culturing. The application of pressure to the cartilage construct improves both the uniformity of seeding throughout the construct and facilitates the flow of nutrients to and removal of waste products from cells embedded in the construct. In this manner, a tissue-engineered cartilage construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of cartilage with normal physiologic function may be formed.

Abstract: The novel gene, Rasp-1, which is up-regulated in regenerating liver, is disclosed. The novel RASP-1 protein, which is encoded by the Rasp-1 gene, is also disclosed. In addition, antibodies against the Rasp-1 gene products are also disclosed. Furthermore, the use of Rasp-1 nucleic acid sequences, Rasp-1 gene products, and antibodies against Rasp-1 gene products in the treatment and diagnosis of liver disorders is also disclosed.

Abstract: A stromal cell-based three-dimensional cell culture system is prepared which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue.

Abstract: A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media, allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.

Abstract: The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF-.beta. in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF-.beta.. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc.

Abstract: Mammalian cells capable of producing cartilage are cultured under a shear flow stress of about 1 to about 100 dynes/cm.sup.2 to produce artificial cartilage for surgical transplantation to replace damaged or missing cartilage. Shear flow stressed cells display enhanced maintenance of chondrocyte phenotype and produce an extracellular matrix containing an enhanced ratio of type II collagen to type I collagen. The cells may be chondrocytes, chondrocyte stem cells or cells such as myoblasts or fibroblasts that transdifferentiate into chondrocytes. A bioreactor is used containing a growth chamber having a substrate on which the cells capable of producing cartilage are attached, and means for applying relative movement between a liquid culture medium and the substrate to provide the shear flow stress. The substrate may be a scaffold, or a nonporous surface such as the surface of a rotatable drum or disc, or the surface of a static plate that supports cell growth in a monolayer.

Abstract: The invention relates to the isolation and use of pre-chondrocytes from the umbilical cord, specifically from Wharton's jelly, that give rise to chondrocytes which produce cartilage. The isolated pre-chondrocytes, or the chondrocytes to which they give rise, can be mitotically expanded in culture and used in the production of new cartilage tissue for therapeutic use. "Banks" of pre-chondrocytes or chondrocytes can be stored frozen, and thawed and used to produce new cartilage tissue as needed.

Abstract: The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF-.beta. in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF-.beta.. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc.

Abstract: A stromal cell-based three-dimensional cell culture system is provided which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells along with connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. Living stromal tissue so formed provides support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue.

Abstract: The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.