Two Or More Cell Types, Per Se, In Co-culture Patents (Class 435/347)
  • Patent number: 11643639
    Abstract: Some embodiments are directed to a method for preparing a skin substitute, a dermal substitute, to a skin substitute, to a dermal substitute and to a kit for implementing the method. Some other embodiments are directed to a graft that can consist of of a skin substitute and to the use thereof as treating a skin disorder and/or a loss of skin substance.
    Type: Grant
    Filed: March 25, 2016
    Date of Patent: May 9, 2023
    Assignees: UNIVERSITÉ DE BORDEAUX, INSERM, CENTRE HOSPITALIER UNIVERSITAIRE DE BORDEAUX
    Inventors: Vincent Casoli, Muriel Cario-André, Jean-Christophe Lepivert
  • Patent number: 11230702
    Abstract: Provided herein is an in vitro model of the blood brain barrier. In some embodiments, the model includes: an endothelial cell layer, and brain tissue layer comprising neuronal cells, and optionally one or more of astrocytes, pericytes, oligodendrocytes, and microglia. In some embodiments, the model further comprises a porous membrane between said endothelial cell layer and the neuronal cell layer. A microfluidic device comprising the same and methods of use thereof are also provided.
    Type: Grant
    Filed: August 4, 2017
    Date of Patent: January 25, 2022
    Assignee: Wake Forest University Health Sciences
    Inventors: Robert T. Wicks, Anthony Atala, Goodwell Nzou, Elizabeth E. Wicks
  • Patent number: 10765704
    Abstract: Disclosed herein are induced hepatocytes from a trophoblast stem cell, methods for inducing the cells, and compositions thereof. Also disclosed herein are methods of treating a disease or disorder (e.g., liver-associated) by utilizing an induced hepatocyte disclosed herein.
    Type: Grant
    Filed: September 15, 2017
    Date of Patent: September 8, 2020
    Assignee: ACCELERATED BIOSCIENCES CORP.
    Inventors: Jau-Nan Lee, Tony Tung-Yin Lee, Yuta Lee, Eing-Mei Tsai
  • Patent number: 10119117
    Abstract: In one embodiment, the present application discloses a cell culture medium for culturing cell lines suitable for producing a therapeutic protein, comprising an amino acid selected from a group consisting of L-arginine, L-asparagine, L-proline, L leucine and L hydroxyproline and a mixture thereof; a vitamin selected from a group consisting of ascorbic acid Mg2+ salt, biotin, pyridoxine HCL, folic acid, riboflavin and D-calcium pantothenate, and a mixture thereof; an element selected from a group consisting of ammonium meta vanadate, sodium meta vanadate, germanium dioxide, barium acetate, aluminum chloride, rubidium chloride, cadmium chloride, ammonium molybedate, stannous chloride, cobalt chloride, chromium sulfate, silver nitrate, sodium metasilicate, zinc sulfate, manganese sulfate H2O, manganous chloride, ferric nitrate 9H2O, ferrous sulfate 7H2O, ferric ammonium citrate, magnesium chloride anhydrous, and magnesium sulfate anhydrous, and a mixture thereof; a nucleoside selected from a group consisting of u
    Type: Grant
    Filed: January 11, 2017
    Date of Patent: November 6, 2018
    Assignee: NANOGEN PHARMACEUTICAL BIOTECHNOLOGY CO., LTD
    Inventors: Nhan Ho, Praveen Gupta, Si Minh Do, Phuong Thi Bich Ho, Ngoc-Thuy Bui, Huy Quang Nguyen, Trang Thi Thuy Nguyen, Ha Thi Hong Truong, Tuan Anh Le
  • Patent number: 10113148
    Abstract: The present invention relates to a method by which cells usable for an immune cell therapy are separated from peripheral blood and grown. The present invention makes it possible to provide immune system cells which are large enough in number to be used in the immune cell therapy.
    Type: Grant
    Filed: July 10, 2013
    Date of Patent: October 30, 2018
    Inventors: Hiroyuki Abe, Hiroaki Kawasaki
  • Patent number: 9862755
    Abstract: The present invention is directed to a high affinity T cell receptor (TCR) against a tumor-associated antigen, an isolated nucleic acid molecule encoding same, a T cell expressing said TCR, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing said tumor-associated antigen.
    Type: Grant
    Filed: March 25, 2014
    Date of Patent: January 9, 2018
    Assignee: MAX-DELBRUECK-CENTRUM FUER MOLEKULARE MEDIZIN
    Inventors: Dolores Jean Schendel, Susanne Wilde, Bernhard Frankenberger, Wolfgang Uckert
  • Patent number: 9709574
    Abstract: The present invention provides for methods of producing human monoclonal antibodies against a wide variety of antigens including bacterial and viral antigens, as well as tumor antigens, and various autoantigens. Also provided are the antibodies themselves, nucleic acids encoding such antibodies, cells producing such antibodies, and methods of using such antibodies for diagnostic assays and passive immunity against disease states such as infection and cancer.
    Type: Grant
    Filed: March 12, 2014
    Date of Patent: July 18, 2017
    Assignee: MUSC Foundation for Research Development
    Inventors: Natalie Sutkowski, Semyon Rubinchik
  • Patent number: 9567568
    Abstract: A method of isolating monocyte populations of cells and inducing apoptosis in these populations without production of pro-inflammatory mediators is disclosed. The method comprises isolating the monocytes and, subjecting them to substrate-adherence and serum deprivation conditions. Apoptotic monocytes as prepared are useful for treating inflammation-associated diseases.
    Type: Grant
    Filed: September 29, 2014
    Date of Patent: February 14, 2017
    Assignee: ENLIVEX THERAPEUTICS LTD.
    Inventor: Dror Mevorach
  • Patent number: 9345726
    Abstract: The present invention provides compositions comprising CD117+ cells and methods for using the same in allograft. In some aspects of the invention, methods are provided for prolonging allograft survival in a subject by administering CD117+ cells.
    Type: Grant
    Filed: September 7, 2010
    Date of Patent: May 24, 2016
    Assignee: The Regents of the University of Colorado, a body corporate
    Inventors: Todd J. Grazia, Martin R. Zamora, Robert J. Plenter
  • Patent number: 9267936
    Abstract: A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more human muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a human muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.
    Type: Grant
    Filed: August 6, 2014
    Date of Patent: February 23, 2016
    Assignee: University of Central Florida Research Foundation
    Inventors: James Hickman, Xiufang Guo
  • Patent number: 9121008
    Abstract: The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.
    Type: Grant
    Filed: August 31, 2005
    Date of Patent: September 1, 2015
    Assignee: University of Utah Research Foundation
    Inventor: Schickwann Tsai
  • Patent number: 9107878
    Abstract: The present invention relates to compositions and methods for treating an animal with a tumor or other metabolic disorder. In particular, the presently disclosed subject matter relates to methods of electroporating exosomes shed by tumors and by other metabolic disorders into immune cells such as dendritic cells and T cells. Administration of the electroporated immune cells to an animal with a tumor results in an increased immune response to the tumor and treatment of the tumor.
    Type: Grant
    Filed: April 6, 2011
    Date of Patent: August 18, 2015
    Assignee: EXOCYTE THERAPEUTICS PTE, LTD
    Inventor: John W. Holaday
  • Publication number: 20150147806
    Abstract: Disclosed is a method for preparing a transferable membrane having a nanometer scale dimension in thickness and pore size by non-solvent vapor-induced phase separation process, comprising spin-casting a polymer solution in a closed humid chamber and controlling the relative humidity (RH) of the chamber using at least one supersaturated salts solution whereby the density of the pores are controlled. Also provided is a TNT membrane prepared by the present method and its use. The present membrane can be advantageously used as co-culture platform facilitating versatile and controllable cell co-culture assays and further allowing the quantitative analysis of paracrine communications between cells for example between cancer cells and different types of stromal cells by providing an in vivo-like environment, which can offer more in-vivo-like results to identify key signaling molecules for therapeutic targets of a disease.
    Type: Application
    Filed: November 20, 2014
    Publication date: May 28, 2015
    Applicant: SNU R&DB FOUNDATION
    Inventors: Kookheon CHAR, Jwa-Min NAM, Yeongseon JANG, Hyojin LEE
  • Publication number: 20150132844
    Abstract: Methods are provided for the production of dendritic cells from monocytes that have been incubated at a temperature of 1° C.-34° C. for a period of approximately 6 to 96 hours from the time they are isolated from a subject. After the incubation period, the monocytes can then be induced to differentiate into dendritic cells. Mature dendritic cells made by the methods of the invention have increased levels of one or more of CD80, CD83, CD86, MHC class I molecules, or MHC class II molecules as compared to mature dendritic cells prepared from monocytes that have not been held at 1° C.-34° C. for at least 6 hours from the time they were isolated from a subject. Dendritic cells made by the methods of the invention are useful for the preparation of vaccines and for the stimulation of T cells.
    Type: Application
    Filed: June 18, 2014
    Publication date: May 14, 2015
    Inventors: Rebecca POGUE, Tamara Monesmith, Irina Tcherepanova, Lois Dinterman
  • Publication number: 20150111240
    Abstract: Methods for mimicking a tumor microenvironment in vitro are provided. The methods comprise indirectly applying a shear stress upon at least one tumor cell type plated on a surface within a cell culture container. Methods for mimicking tumor metastasis and methods for testing drugs or compounds in such systems are also provided.
    Type: Application
    Filed: October 21, 2014
    Publication date: April 23, 2015
    Inventors: Brian R. Wamhoff, Brett R. Blackman, Robert A. Figler, Daniel G. Gioeli, Michael B. Simmers
  • Patent number: 8999652
    Abstract: Mixtures of cell types can be analyzed by having at least two signal markers, with at least one at three different levels to provide a barcode for each cell type. The mixture of cells may be subjected to a common candidate moiety and the effect of the moiety on the cells determined along with identification of the cell by the barcode. Conveniently, surface marker proteins and labeled antibodies can be used to create the barcode and the cells analyzed with flow cytometry.
    Type: Grant
    Filed: August 5, 2008
    Date of Patent: April 7, 2015
    Assignee: Primity Bio, Inc.
    Inventors: Peter Oliver Krutzik, Thomas Scott Wehrman
  • Publication number: 20150093428
    Abstract: A 3D in vitro bi-phasic cartilage-bone organoid includes a layer of an artificial cartilage tissue, and a layer of an artificial bone tissue comprising a structure-giving scaffold and a bone marrow structure. The layer of the artificial cartilage tissue contacts at least one surface of the layer of the artificial bone tissue.
    Type: Application
    Filed: February 28, 2013
    Publication date: April 2, 2015
    Applicant: TISSUSE GMBH
    Inventors: Mark Rosowski, Shirin Fatehi-Varkani, Roland Lauster, Uwe Marx
  • Publication number: 20150079143
    Abstract: Methods of making a biologically active three-dimensional scaffold capable of supporting growth and differentiation of a cell are described. Biologically active three-dimensional scaffold made by the methods of the invention and an engineered tissue made from the scaffolds are described. Fibers of desired porosity can be obtained from non-structural ECM by lyophilization and/or electrospinning which can be useful for numerous tissue engineering applications requiring complex scaffolds, such as wound healing, artificial skin (burns), soft tissue replacement/repair and spinal cord injury.
    Type: Application
    Filed: November 18, 2014
    Publication date: March 19, 2015
    Inventors: Peter I. Lelkes, Mengyan Li, Anat Perets, Honesto Poblete, Philip Lazarovici
  • Publication number: 20150079673
    Abstract: The present disclosure provides a human hepatocyte co-culture which maintains the phenotype of cells from human donors with diabetes, and methods of using same. The hepatocyte co-culture system provides an in vitro model in which both cell viability and phenotype are maintained for extended periods relative to primary human hepatocyte monocultures, and is used in methods for high throughput screening and evaluation of drug candidates, and kits for performing such testing.
    Type: Application
    Filed: July 3, 2014
    Publication date: March 19, 2015
    Inventors: Salman R. Khetani, Michael D. Lehrer
  • Publication number: 20150079674
    Abstract: The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to a novel human embryo co-culture system to improve human embryo growth in vitro and, consequently, increase pregnancy rates in infertile women undergoing in vitro fertilization (IVF) treatment. More particularly, the present invention relates to a method of growing an embryo to a blastocyst stage of development comprising the step of coculturing said embryo in the presence of a population of cumulus cells.
    Type: Application
    Filed: November 5, 2014
    Publication date: March 19, 2015
    Inventors: Samir HAMAMAH, Said ASSOU
  • Publication number: 20150072413
    Abstract: Cell culture apparatus comprising at least two adjacent cell cultivation channels separated by a permeable or semipermeable membrane, wherein at least one channel, for the majority of its length, has a cross sectional area of no more than 1 mm2, said channel being provided with entrance and exit means to permit the passage of media therethrough, allows co-culture of separate cell types, e.g. human and microbial cells, without mingling, allowing monitoring of cell cultures and chemical exchanges between the respective cell cultures.
    Type: Application
    Filed: March 27, 2013
    Publication date: March 12, 2015
    Inventors: Frederic Zenhausern, Matthew Estes, Paul Wilmes, Pranjul Shah
  • Publication number: 20150064781
    Abstract: Cells derived from postpartum umbilicus and placenta are disclosed. Pharmaceutical compositions, devices and methods for the regeneration or repair of ocular tissue using the postpartum-derived cells are also disclosed.
    Type: Application
    Filed: July 28, 2014
    Publication date: March 5, 2015
    Inventors: Sanjay MISTRY, Darin MESSINA
  • Publication number: 20150065389
    Abstract: The present invention is drawn to the generation of micropatterns of biomolecules and cells on standard laboratory materials through selective ablation of a physisorbed biomolecule with oxygen plasma. In certain embodiments, oxygen plasma is able to ablate selectively physisorbed layers of biomolecules (e.g., type-I collagen, fibronectin, laminin, and Matrigel) along complex non-linear paths which are difficult or impossible to pattern using alternative methods. In addition, certain embodiments of the present invention relate to the micropatterning of multiple cell types on curved surfaces, multiwell plates, and flat bottom flasks. The invention also features kits for use with the subject methods.
    Type: Application
    Filed: March 26, 2014
    Publication date: March 5, 2015
    Applicant: Massachusetts Institute of Technology
    Inventors: David T. Eddington, Sangeeta N. BHATIA
  • Publication number: 20150050730
    Abstract: The present invention refers to a process of ex vivo expansion of stem cells, in a bioreactor, in particular hematopoietic stem/progenitor cells co-cultured with mesenchymal stem cells immobilized on microcarriers, for transplantation. The process comprises the steps of: a) forming a suspension of mesenchymal stem cells immobilized on microcarriers, b) inoculating in a bioreactor containing an expansion medium, hematopoietic cells co-cultured with mesenchymal stem cells immobilized on microcarriers c) expansion of hematopoietic cells. The process of the invention is capable of being implemented in a Kit.
    Type: Application
    Filed: March 19, 2013
    Publication date: February 19, 2015
    Inventors: Joaquim Manuel Sampaio Cabral, Claudia Alexandra Martins Lobato da Silva, Pedro Miguel Zacarias Andrade, Francisco Ferreira dos Santos, Maria da Graca Nortadas Duarte de Almeida-Porada
  • Patent number: 8927273
    Abstract: The present invention provides a method for preparing a cytotoxic lymphocyte characterized in that the method comprises the step of carrying out at least one step selected from induction, maintenance and expansion of a cytotoxic lymphocyte using a medium containing serum and plasma at a total concentration of 0% by volume or more and less than 5% by volume, in the presence of fibronectin, a fragment thereof or a mixture thereof.
    Type: Grant
    Filed: August 19, 2004
    Date of Patent: January 6, 2015
    Assignee: Takara Bio Inc.
    Inventors: Mitsuko Ideno, Nobuko Muraki, Kinuko Ogawa, Masayuki Kishimoto, Tatsuji Enoki, Hiroaki Sagawa, Ikunoshin Kato
  • Patent number: 8916380
    Abstract: Disclosed is a method for preparing an embryonic stem cell (ESC)-like cell, which includes the steps of: (a) obtaining a first cell population from a mammalian tissue or body fluid, wherein the first cell population comprises adult stem cells; (b) obtaining a second somatic cell population from a mammalian tissue, wherein the mammalian tissue is different from the mammalian tissue in step (a) and the second cell population is different from the first cell population; (c) coculturing the first cell population and the second cell population in a medium for a period of time sufficient to form a colony from either the first cell population or the second cell population; and (d) subculturing a cell from the colony in a medium for a period time sufficient to prepare the ESC-like cell.
    Type: Grant
    Filed: December 20, 2006
    Date of Patent: December 23, 2014
    Assignee: Seoul National University Industry Foundation
    Inventors: Jeong Mook Lim, Jae Yong Han, Hee Bal Kim, Seoung Tae Lee, Eun Ju Lee, Seung Pyo Gong
  • Patent number: 8906678
    Abstract: The disclosure relates to methods of binding and identifying undifferentiated pluripotent stem cells and particularly, although not exclusively, to use of binding moieties which bind to PHB on the surface of undifferentiated pluripotent stem cells, such as PHB-binding peptides, and to methods for depleting undifferentiated stem cells from a sample.
    Type: Grant
    Filed: March 10, 2011
    Date of Patent: December 9, 2014
    Assignee: Agency for Science, Technology and Research
    Inventors: Boon Hwa Andre Choo, Wey Jia Fong
  • Publication number: 20140349312
    Abstract: The present invention relates to a culture support for cultivating hematopoietic stem cells (HSCs) and/or hematopoietic progenitors (HPs), comprising a calcium biomaterial, osteoclasts, endothelial cells and mesenchymatous stem cells (MSCs) and/or osteoblasts and/or adipocytes. The present invention also relates to a method for preparing such a culture support, and an in vitro HSC and/or HP cultivation method. The use of such a culture support for studying cellular mechanisms involved in hematopoiesis and/or differentiation of HSC/HPs and/or for studying the efficacy and/or the toxicity of a medicament candidate is also described.
    Type: Application
    Filed: August 14, 2012
    Publication date: November 27, 2014
    Applicants: Institut Nationalde la Sante et de la Recherche Medicale (INSERM), ETAT FRANCAIS (MINISTERE DE LA DEFENSE), SERVICE DE SANTE DES ARMEES
    Inventors: Jean-Jacques Lataillade, Marie-Caroline Le Bousse-Kerdiles
  • Publication number: 20140335062
    Abstract: Co-culturing of mesenchymal stem cells or tissues comprising mesenchymal stem cells with myocytes or myocyte containing tissues provide for the long term culture and expansion of myocytes. The co-culture gives rise to three-dimensional functioning cardiac tissue grafts or constructs.
    Type: Application
    Filed: January 18, 2013
    Publication date: November 13, 2014
    Inventor: Joshua M. Hare
  • Publication number: 20140335610
    Abstract: A cell culture substrate is used comprising a photopolymerization initiator immobilized on a surface of the cell culture substrate, and a linear polymer immobilized on a part or the entirety of the surface via the photopolymerization initiator, and wherein the photopolymerization initiator is thioxanthone. Thereby, advantageously, a single type or multiple types of cells are efficiently cultured on specific regions of the culture substrate, and efficiently detached only by changing temperature on the surface of the substrate.
    Type: Application
    Filed: November 20, 2012
    Publication date: November 13, 2014
    Applicant: TOKYO WOMEN'S MEDICAL UNIVERSITY
    Inventors: Kazuhiro Fukumori, Yoshikatsu Akiyama, Masayuki Yamato, Teruo Okano
  • Patent number: 8871461
    Abstract: Methods and devices for applying hemodynamic patterns to human/animal cells in culture are described. Hemodynamic flow patterns are measured directly from the human circulation and translated to a motor that controls the rotation of a cone. The cone is submerged in fluid (i.e., cell culture media) and brought into close proximity to the cells. Rotation of the cone creates time-varying shear stresses. This model closely mimics the physiological hemodynamic forces imparted on endothelial cells in vivo. A TRANSWELL coculture dish (i.e., a coculture dish comprising an artificial porous membrane) may be incorporated, permitting two, three, or more different cell types to be physically separated within the culture dish environment. In-flow and out-flow tubing may be used to supply media, drugs, etc. separately and independently to both the inner and outer chambers. The physical separation of the cell types permits each cell type to be separately isolated for analysis.
    Type: Grant
    Filed: October 11, 2010
    Date of Patent: October 28, 2014
    Assignee: Hemoshear, LLC
    Inventors: Brett R. Blackman, Brian R. Wamhoff
  • Patent number: 8858934
    Abstract: The present invention relates to a method of producing cells having at least one characteristic of human hepatocytes as well as to cells produced by said method and uses of these cells.
    Type: Grant
    Filed: August 11, 2011
    Date of Patent: October 14, 2014
    Assignee: ABAG Verwaltungs GmbH
    Inventors: Alexander Gerbes, Andreas Benesic
  • Publication number: 20140302599
    Abstract: The invention provides a method of co-culturing mammalian muscle cells and mammalian motoneurons. The method comprises preparing one or more carriers coated with a covalently bonded monolayer of trimethoxysilylpropyl diethylenetriamine (DETA); suspending isolated fetal mammalian skeletal muscle cells in serum-free medium according to medium composition 1; suspending isolated fetal mammalian spinal motoneurons in serum-free medium according to medium composition 1; plating the suspended muscle cells onto the one or more carriers at a predetermined density and allowing the muscle cells to attach; plating the suspended motoneurons at a predetermined density onto the one or more carriers and allowing the motoneurons to attach; covering the one or more carriers with a mixture of medium composition 1 and medium composition 2; and incubating the carriers covered in the media mixture.
    Type: Application
    Filed: June 9, 2014
    Publication date: October 9, 2014
    Applicant: UNIVERSITY OF CENTRAL FLORIDA RESEARCH FOUNDATION, INC.
    Inventors: James Hickman, Mainak DAS
  • Publication number: 20140286912
    Abstract: The present disclosure relates to discogenic cell populations, methods of deriving, and methods of using them. The presently described discogenic cell populations may be used to restore or regenerate damaged, diseased, or missing intervertebral discs of a subject. The presently described discogenic cell populations can be derived from and administered or implanted into a subject, or may be derived from an unrelated donor.
    Type: Application
    Filed: March 14, 2014
    Publication date: September 25, 2014
    Applicant: DiscGenics, Inc.
    Inventors: Lara Ionescu Silverman, Kevin T. Foley
  • Publication number: 20140287960
    Abstract: Engineered, living, three-dimensional liver tissue constructs comprising: one or more layers, wherein each layer contains one or more liver cell types, the one or more layers cohered to form a living, three-dimensional liver tissue construct. In some embodiments, the constructs are characterized by having at least one of: at least one layer comprising a plurality of cell types, the cell types spatially arranged relative to each other to create a planar geometry; and a plurality of layers, at least one layer compositionally or architecturally distinct from at least one other layer to create a laminar geometry. Also disclosed are arrays and methods of making the same. Also disclosed are engineered, living, three-dimensional liver tissue constructs for use in the augmentation or restoration of one or more liver functions, by in vivo delivery of tissue or utilization of tissue in an extracorporeal device.
    Type: Application
    Filed: June 3, 2014
    Publication date: September 25, 2014
    Applicant: Organovo, Inc.
    Inventors: Benjamin R. Shepherd, Justin B. Robbins, Vivian A. Gorgen, Sharon C. Presnell
  • Publication number: 20140287495
    Abstract: The present invention relates to methods of inducing differentiation of stem cells. In particular, the invention relates to methods of inducing differentiation of embryonic stem cells into muscle cells or vascular endothelial cells. The invention also includes cells, cell lines, testing models and culture systems used in the methods of the present invention and differentiated cells produced therefrom. The present invention also provides methods of using the differentiated cells of the present invention for therapeutic purposes.
    Type: Application
    Filed: March 25, 2014
    Publication date: September 25, 2014
    Applicant: ES Cell International Pte LTD
    Inventor: Christine Lindsay Mummery
  • Publication number: 20140274802
    Abstract: Engineered, living, three-dimensional liver tissue constructs comprising: one or more layers, wherein each layer contains one or more liver cell types, the one or more layers cohered to form a living, three-dimensional liver tissue construct. In some embodiments, the constructs are characterized by having at least one of: at least one layer comprising a plurality of cell types, the cell types spatially arranged relative to each other to create a planar geometry; and a plurality of layers, at least one layer compositionally or architecturally distinct from at least one other layer to create a laminar geometry. Also disclosed are arrays and methods of making the same. Also disclosed are engineered, living, three-dimensional liver tissue constructs for use in the augmentation or restoration of one or more liver functions, by in vivo delivery of tissue or utilization of tissue in an extracorporeal device.
    Type: Application
    Filed: March 15, 2013
    Publication date: September 18, 2014
    Applicant: ORGANOVO, INC.
    Inventors: Benjamin R. Shepherd, Justin B. Robbins, Vivian A. Gorgen, Sharon C. Presnell
  • Patent number: 8835168
    Abstract: A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more human muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a human muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.
    Type: Grant
    Filed: May 6, 2011
    Date of Patent: September 16, 2014
    Assignee: University of Central Florida Research Foundation, Inc.
    Inventors: James Hickman, Xiufang Guo
  • Patent number: 8815584
    Abstract: The invention provides a method of co-culturing mammalian muscle cells and mammalian motoneurons. The method comprises preparing one or more carriers coated with a covalently bonded monolayer of trimethoxysilylpropyl diethylenetriamine (DETA); suspending isolated fetal mammalian skeletal muscle cells in serum-free medium according to medium composition 1; suspending isolated fetal mammalian spinal motoneurons in serum-free medium according to medium composition 1; plating the suspended muscle cells onto the one or more carriers at a predetermined density and allowing the muscle cells to attach; plating the suspended motoneurons at a predetermined density onto the one or more carriers and allowing the motoneurons to attach; covering the one or more carriers with a mixture of medium composition 1 and medium composition 2; and incubating the carriers covered in the media mixture.
    Type: Grant
    Filed: April 23, 2010
    Date of Patent: August 26, 2014
    Assignee: University of Central Florida Research Foundation, Inc.
    Inventors: James J. Hickman, Mainak Das
  • Publication number: 20140237633
    Abstract: The present invention is long-term cultures of avian PGCs and techniques to produce germline chimeric and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. These germline chimeric birds do not have substantial contributions of PGC-derived phenotypes in somatic cells or tissues. This invention includes compositions comprising long-term cultures of PGCs that can be genetically modified by gene targeting, that can accept large amounts of foreign DNA and that contribute to the germline of recipient embryos.
    Type: Application
    Filed: January 24, 2014
    Publication date: August 21, 2014
    Inventors: Marie-Ceclie Van de Lavoir, Philip Albert Leighton
  • Publication number: 20140235933
    Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitor factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.
    Type: Application
    Filed: February 20, 2014
    Publication date: August 21, 2014
    Inventors: Jeffrey D. Lee, Wojtek Auerbach, David Heslin, David Frendewey, Ka-Man Venus Lai, David M. Valenzuela
  • Publication number: 20140228970
    Abstract: An inkjet printing method, system, and computer-usable tangible storage device to print cells and biomaterials for three-dimensional cellular scaffolds and engineered skin grafts are disclosed. The process simultaneously deposits living cells, nutrients, growth factors, therapeutic drugs along with biomaterial scaffolds at the right time and location. This technology can also be used for the microvasculature fabrication using appropriate human microvascular endothelial cells and fibrin to form the microvasculature. When printing human microvascular endothelial cells in conjunction with the fibrin, the cells aligned themselves inside the channels and proliferated to form confluent linings. The 3D tubular structure was also found in the printed patterns. Simultaneously printing biological materials to form a three-dimensional cellular scaffold promotes human microvascular endothelial cell proliferation and microvasculature formation.
    Type: Application
    Filed: February 13, 2013
    Publication date: August 14, 2014
    Inventor: Thomas Boland
  • Patent number: 8802432
    Abstract: Methods of promoting liver morphogenesis prior to the functioning of blood vessels by culturing liver cells with endothelial cells is provided. Also provided are cell cultures and method of promoting vasculogenesis of liver tissue by contacting liver cells with endothelial cells.
    Type: Grant
    Filed: September 6, 2002
    Date of Patent: August 12, 2014
    Assignee: Fox Chase Cancer Center
    Inventors: Kenneth S. Zaret, Kunio Matsumoto, Hideyuki Yoshitomi
  • Publication number: 20140219972
    Abstract: Methods of regenerating tissue using progenitor cells in combination with primary cells from a target tissue are disclosed. In particular, progenitor cells catalyze proliferation and tissue production by primary cells allowing the use of fewer primary cells from a target tissue for effective tissue regeneration. Cell-based therapies combining progenitor cells and primary cells can be used for repair and regeneration of damaged tissue and organs for treating bodily injuries and degenerative diseases. For example, adipose-derived stem cells and neonatal articular chondrocytes, co-encapsulated in mixed or bilayered cultures in a hydrogel comprising chondroitin sulfate methacrylate and poly(ethylene)glycol diacrylate, generated cartilage that could be used for treatment of traumatic injuries or diseases involving cartilage degeneration.
    Type: Application
    Filed: February 5, 2014
    Publication date: August 7, 2014
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Janice Lai, William Maloney, R. Lane Smith, Fan Yang
  • Publication number: 20140212918
    Abstract: The present invention relates to a system and methods for identifying a compound for de-fatting and functional recovery of macrosteatotic hepatocytes.
    Type: Application
    Filed: January 31, 2014
    Publication date: July 31, 2014
    Applicant: Rutgers, The State University of New Jersey
    Inventors: Martin L. Yarmush, Nir I. Nativ, Francois Berthiaume, Gabriel A. Yarmush, Tim Maguire, Rene S. Schloss
  • Publication number: 20140206029
    Abstract: The present invention relates to a tubule forming platform and an in vitro cardiovascular model for use in pharmacological studies. Furthermore, the invention relates to methods for the preparation said platform and model, and to a method of determining a biological activity of a test substance in said platform and cardiovascular model. Still further, the invention relates to an implantable cardiac structure for use in the treatment of cardiac disorders.
    Type: Application
    Filed: June 14, 2012
    Publication date: July 24, 2014
    Applicant: TAMPEREEN YLIOPISTO
    Inventors: Katriina Aalto-Setälä, Tuula Heinonen, Erja Kerkelä, Jertta-Riina Sarkanen, Hanna Vuorenpää, Timo Ylikomi
  • Patent number: 8778330
    Abstract: The present invention relates to methods of generating an ex vivo tissue-like system in a bioreactor system capable of supporting continuous production of, and output of cells and tissues and an ex vivo tissue system made therefrom.
    Type: Grant
    Filed: March 11, 2013
    Date of Patent: July 15, 2014
    Assignee: Aastrom Biosciences, Inc.
    Inventors: Lee Noll, Brian Hampson, Kristin Goltry, Samantha Snabes
  • Patent number: 8765467
    Abstract: Methods are provided for producing novel multicellular compositions comprising cancer cells together with pluripotent human stem cells, which are capable of proliferating and differentiating into various normal cell lines and tissue structures. These novel multicellular compositions are useful for investigating the properties of cancer cells in a normal human tissue microenvironment, and for studying interventions that will modulate these properties including devising, testing and screening therapeutic drugs.
    Type: Grant
    Filed: May 5, 2004
    Date of Patent: July 1, 2014
    Assignee: Technion Research and Development Foundation Ltd.
    Inventors: Karl L. Skorecki, Maty Tzukerman
  • Patent number: 8765468
    Abstract: A device, and method of making the device, capable of therapeutic treatment and/or for in vitro testing of human skin. The device may be used on skin wounds for burned, injured, or diseased skin, and provides structures and functions as in normal uninjured skin, such as barrier function, which is a definitive property of normal skin. The device contains cultured dermal and epidermal cells on a biocompatible, biodegradable reticulated matrix. All or part of the cells may be autologous, from the recipient of the cultured skin device, which advantageously eliminates concerns of tissue compatibility. The cells may also be modified genetically to provide one or more factors to facilitate healing of the engrafted skin replacement, such as an angiogenic factor to stimulate growth of blood vessels.
    Type: Grant
    Filed: May 24, 2013
    Date of Patent: July 1, 2014
    Assignees: University of Cincinnati, Shriners Hospitals for Children
    Inventor: Steven T. Boyce
  • Patent number: 8764828
    Abstract: A system and method for forming a bone construct include providing bone marrow stromal cells on a substrate without disposing the cells within an exogenous scaffold, and culturing the cells in vitro in osteogenic media such that the cells form a confluent monolayer and detach from the substrate to form a self-organized three-dimensional bone construct. A system and method for forming a ligament construct using fibrogenic media and a system and method for forming a functionally integrated bone-ligament construct are also provided.
    Type: Grant
    Filed: February 4, 2008
    Date of Patent: July 1, 2014
    Assignee: The Regents of the University of Michigan
    Inventors: Ellen M. Arruda, Lisa M. Larkin, Fatima N. Syed-Picard, Michael Smietana, Jinjin Ma