Method Of Culturing Encapsulated Cells Patents (Class 435/382)
  • Patent number: 7312085
    Abstract: The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system.
    Type: Grant
    Filed: April 1, 2003
    Date of Patent: December 25, 2007
    Assignee: Fluidigm Corporation
    Inventors: Hou-Pu Chou, Antoine Daridon, Kevin Farrell, Brian Fowler, Yish-Hann Liau, Ian D. Manger, Hany Ramez Nassef, William Throndset
  • Patent number: 7297538
    Abstract: The invention features an encapsulated cell indicator system that includes (a) indicator cells having a signal-responsive element operably linked to a reporter gene; (b) encapsulating material; and (c) a permeable membrane. In this encapsulated cell indicator system, the indicator cells are encapsulated in the encapsulated material and the encapsulated material and the indicator cells are surrounded by the permeable membrane.
    Type: Grant
    Filed: April 12, 2002
    Date of Patent: November 20, 2007
    Assignee: Cardio3 S.A.
    Inventors: Ike W. Lee, Jeffrey D. Croissant, Rabia Ballica
  • Patent number: 7297331
    Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.
    Type: Grant
    Filed: August 16, 2004
    Date of Patent: November 20, 2007
    Assignee: The Rogosin Institute
    Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
  • Patent number: 7238526
    Abstract: Methods for efficient production of recombinant AAV employ a host cell which comprising AAV rep and cap genes stably integrated within the cell's chromosomes, wherein the AAV rep and cap genes are each operatively linked to regulatory sequences capable of directing the expression of the rep and cap gene products upon infection of the cell with a helper virus, a helper gene, and a helper gene product. A method for producing recombinant adeno-associated virus (rAAV) involves infecting such a host cell with a helper virus, gene or gene product and infecting the infected host cell with a recombinant hybrid virus or plasmid vector containing adenovirus cis-elements necessary for replication and virion encapsidation, AAV sequences comprising the 5? and 3? ITRs of an AAV, and a selected gene operatively linked to regulatory sequences directing its expression, which is flanked by the above-mentioned AAV sequences.
    Type: Grant
    Filed: September 11, 2002
    Date of Patent: July 3, 2007
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: James M. Wilson, Guangping Gao
  • Patent number: 7229808
    Abstract: The present invention relates to a process for producing a bioreactor using viable immobilized biological material and to the bioreactor itself. More particularly, the present invention relates to a process for producing a siliceous layer capable of biomass immobilization and selectively cutting off macromolecules having a molecular weight higher than a selected threshold, comprising the steps of: a) supplying a gas flow of a gas carrier saturated by a mixture of silicon alkoxides selected from the group comprising (1)Si(OR)4, (2)SiH(OR)3, (3)R?Si(OR)3 and (4)R?SiH(OR)2 wherein R and R?, equal or different each other, are alkyl and/or aryl groups, wherein said gas flow is prepared by bubbling the gas carrier into a liquid mixture of said alkoxides in the ratio of (1)40–85/(2)0–60/(3)0–60/(4)0–60 (% v/v), preferably in the ratio of (1)40–85/(2)0–50/(3)0–50/(4)0–50 (% v/v), more preferably in the ratio of (1)50–80/(2)0–20/(3)5–30/(4)5–30 (% v/v), at a temperature of from 20 to 180° C.
    Type: Grant
    Filed: January 18, 2002
    Date of Patent: June 12, 2007
    Assignee: Silbiotec Due S.A.
    Inventors: Gianni Carturan, Roberto Dal Toso, Renzo Dal Monte
  • Patent number: 7192769
    Abstract: The invention relates to a method for lymphoid tissue-specific cell production from hematopoietic progenitor cells in unique, three-dimensional culture devices, in the presence of antigen presenting cells and lymphoreticular stromal cells, and in the absence of exogenously added growth factors. The resulting lymphoid tissue-specific cells may be isolated at any sequential stage of differentiation and further expanded. The lymphoid tissue-specific cells also may be genetically altered at any stage of the process.
    Type: Grant
    Filed: May 31, 2002
    Date of Patent: March 20, 2007
    Assignee: Cytomatrix, LLC
    Inventors: Mark J. Pykett, Michael Rosenzweig, David T. Scadden, Mark C. Poznansky
  • Patent number: 7101545
    Abstract: There is provided a method for growing human intervertebral cells. Disc tissue is surgically removed from a normal disc of a patient, the cells expanded by feeding with a cell stimulant such as a growth factor, or a cytokine or a bioactive agent to form monolayer primary cell cultures on a plastic mesh such as a nylon mesh. In the case of a growth factor, fetal bovine serum is preferred as it improves cell proliferation and production of appropriate extracellular matrix components. In another aspect of this invention, the monolayer primary cell cultures are seeded in alginate or agarose and fed again with the cell stimulant until three-dimensional cell cultures are formed. The cells are recovered from the alginate or agarose or from monolayer cultures. Re-implantation is carried out using bioresorbable carriers or cell suspensions.
    Type: Grant
    Filed: April 27, 2000
    Date of Patent: September 5, 2006
    Assignees: Charlotte-Mecklenburg Hospital Authority, Carolinas Medical Center
    Inventors: Edward Nathaniel Hanley, Jr., Helen Elizabeth Gruber
  • Patent number: 7056726
    Abstract: The invention concerns a semipermeable chamber for encapsulation of cells producing at least a biological substance of interest, characterised in that it consists of a porous polycarbonate biocompatible film modified at the surface by generated polar sites and covered with at least a layer of hydrophilic polymer.
    Type: Grant
    Filed: January 29, 2002
    Date of Patent: June 6, 2006
    Assignees: Association pour les Transferts de Technologies du Mans, Universite Catholique de louvain, Centre Europeen d'Etude du Diabete (CEED)
    Inventors: Gilbert Legeay, Patrick Bertrand, Alain Belcourt, Laurence Kessler
  • Patent number: 7041504
    Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.
    Type: Grant
    Filed: December 12, 2000
    Date of Patent: May 9, 2006
    Assignee: The Rogosin Institute
    Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
  • Patent number: 6972194
    Abstract: The invention relates to the field of medicine and more particularly it relates to the problem of vaccination against tumor cells and vaccinotherapy of oncological diseases, and also to a method of treating diabetes mellitus. In the invention a new method of cultivating cells is proposed, which contemplates forming a capsule of a polyacrylamide gel in the tissue of an animal, including a human, into which capsule desirable cells are injected. The invention provides for maintaining the viability of cells during a long period of time.
    Type: Grant
    Filed: November 22, 2000
    Date of Patent: December 6, 2005
    Inventors: Dmitry Vladimirovich Zybin, Alexei Gennadievich Kotelevits, Vladimir Konstantinovich Sologub, Ljubov Leonidovna Mironova, Sergei Evgenievich Severin
  • Patent number: 6893634
    Abstract: The present invention relates to capsules encapsulating cytochrome P450 producing cells and cytochrome P450 producing retroviral packaging cells. Furthermore, the present invention relates to the treatment of cancer or any other relevant disease with said capsules and to the use of said capsules for the preparation of a pharmaceutical composition for said treatment.
    Type: Grant
    Filed: September 24, 1998
    Date of Patent: May 17, 2005
    Assignees: GSF-Forschungszentrum fur Umwelt und Gesundheit GmbH, Bavarian Nordic A/S
    Inventors: Walter H. Günzburg, Peter Karle, Robert Saller, Brian Salmons, Matthias Löhr, Peter Müller
  • Patent number: 6872387
    Abstract: Methods and compositions are described that provide scaffolds for the support of cells. The scaffolds of the present invention have structural uniformity and desirable mechanical properties that make them suitable for a variety of uses, including uses for in vitro tissue regeneration or in vivo tissue or organ replacement. A method is described for controlling three-dimensional structure of the hydrogel/cell constructs under tissue culture environment.
    Type: Grant
    Filed: February 23, 1999
    Date of Patent: March 29, 2005
    Assignee: The Regents of the University of Michigan
    Inventor: Peter X. Ma
  • Patent number: 6872569
    Abstract: The present invention relates to a method of in vitro spermatogenesis involving Sertoli cells and diploid germ cells from a testis of a male mammal to yield differentiated haploid spermatids. The present invention also relates to spermatids produced by the method described above, where the spermatids are haploid. The present invention also involves a method of overcoming male infertility in mammals involving the use of the haploid round spermatids produced by the in vitro spermatogenesis method of the present invention. The present invention also relates to isolated haploid spermatids.
    Type: Grant
    Filed: May 16, 2002
    Date of Patent: March 29, 2005
    Assignee: Cornell Research Foundation, Inc.
    Inventors: Dong Ryul Lee, Michael T. Kaproth, John E. Parks
  • Patent number: 6846675
    Abstract: The present invention relates to in vitro cultured skin substitutes, and in particular to improved methods for organotypic culture of skin substitutes. In some embodiments, the dermal equivalent of the skin substitute is lifted to air interface of the culture prior to seeding with keratinocytes. In other embodiments, increased concentrations of collagen are used to form the dermal equivalent. In still other embodiments, optimized media are utilized to maintain the skin equivalents.
    Type: Grant
    Filed: March 1, 2002
    Date of Patent: January 25, 2005
    Assignee: Stratech Corporation
    Inventors: Paul Barth Conrad, Cathy Ann-Rusmussen Ivarie, Lynn Allen-Hoffmann
  • Patent number: 6818230
    Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.
    Type: Grant
    Filed: January 3, 2003
    Date of Patent: November 16, 2004
    Assignee: The Rogosin Institute
    Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
  • Patent number: 6808705
    Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.
    Type: Grant
    Filed: January 3, 2003
    Date of Patent: October 26, 2004
    Assignee: The Rogosin Institute
    Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
  • Publication number: 20040209359
    Abstract: A freeze-dried biocompatible matrix that includes plasma proteins that are useful as implants for tissue engineering as well as in biotechnology. Methods of producing the matrix are also provided. Mechanical and physical parameters can be controlled by the use of auxiliary components or additives which may be removed after the matrix is formed in order to improve the biological properties of the matrix. These matrices may be used clinically per se or as a cell-bearing implant.
    Type: Application
    Filed: January 20, 2004
    Publication date: October 21, 2004
    Inventors: Avner Yayon, Rachel Glicklis
  • Patent number: 6790441
    Abstract: According to the present invention, there is provided a biological chamber system having a biochamber defined by outer walls of Sertoli cells. Also provided is a transplantation facilitator including a biochamber. A method of making biochambers by co-culturing facilitator cells and therapeutic cells and then aggregating the facilitator celes is also provided. Also provided is a method of transplanting cells by incorporating transplant cells into a biochamber and transplanting the biochamber containing the transplant cells.
    Type: Grant
    Filed: June 13, 2000
    Date of Patent: September 14, 2004
    Assignee: University of South Florida
    Inventors: Don F. Cameron, Paul R. Sanberg, Samuel Saporta, Joelle J. Hushen
  • Patent number: 6783964
    Abstract: Methods of treating and forming biocompatible microcapsules that contain living cells are provided, to improve the function of the microcapsules. In particular, methods of treating islet cells or microcapsules containing islet cells are provided. Culture of isolated islet cells prior to encapsulation, culture of encapsulated cells, and cryopreservation of islet cells prior to encapsulation, are described. Methods for harvesting viable islets that incorporates an anti-oxidant in the digestion medium are also disclosed.
    Type: Grant
    Filed: January 23, 2002
    Date of Patent: August 31, 2004
    Assignee: Duke University
    Inventor: Emmanuel C. Opara
  • Patent number: 6780643
    Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.
    Type: Grant
    Filed: December 12, 2000
    Date of Patent: August 24, 2004
    Assignee: The Rogosin Institute
    Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
  • Patent number: 6730314
    Abstract: A process is provided for the production of a human cartilage implant from chondrocytes cultured in vitro, which come as close as possible to the original with respect to their biochemical composition and biomechanical properties. Up to 20% vol. of human serum is used as medium addition in the process. The chondrocytes can be kept in monolayer culture until the 12th passage in order firstly to be re-differentiated, incubated under a reduced oxygen partial pressure, and subsequently stimulated to form a three-dimensional cartilage tissue due to aggregation under an oxygen partial pressure of 21%. In an embodiment, chondrocytes in alginate beads are cultured in a nutrient solution, which may contain human serum and one or more chondrogenic growth factors, under an oxygen partial pressure of less than 20 volume %, isolated from the alginate beads by a treatment with a chelating agent, aggregated by centrifugation and cultured under an oxygen partial pressure of: −21 volume %.
    Type: Grant
    Filed: August 29, 2001
    Date of Patent: May 4, 2004
    Assignee: Merck Patent Gesellschaft
    Inventors: Brigitte Jeschke, Jörg Meyer, Peter Adamietz, Norbert Meenen, Christiane Göpfert
  • Patent number: 6713293
    Abstract: The present invention provides a drug delivery device comprising encapsulated cells that contain multiple copies of an expression cassette. The drug delivery device of the present invention is useful to supply an animal, including a human, with a therapeutically desirable molecule, including physiological activities lacking in disease conditions or antagonist against conditions in an animal, especially a human.
    Type: Grant
    Filed: February 8, 1999
    Date of Patent: March 30, 2004
    Inventors: Friedrich Grummt, Birgitta Sauer, Martha Müller
  • Patent number: 6703017
    Abstract: The subject invention concerns new methods which make it possible, for the first time, to grow functional islet-producing stem cells (IPSCs), islet progenitor cells (IPCs) and IPC-derived islets (IdIs) in in vitro cultures. The subject invention also concerns the use of the in vitro grown IPSCs, IPCs and/or IdIs for implantation into a mammal for in vivo therapy of diabetes. The subject invention further concerns a process of using the implanted cells for growing a pancreas-like structure in vivo that has the same functional, morphological and histological characteristics as those observed in normal pancreatic endocrine tissue. The ability to grow these cells in vitro and pancreas-like structures in vivo opens up important new avenues for research and therapy relating to diabetes.
    Type: Grant
    Filed: September 27, 1999
    Date of Patent: March 9, 2004
    Assignees: Ixion Biotechnology, Inc., University of Florida
    Inventors: Ammon B. Peck, Janet Cornelius, Vijayakumar K. Ramiya
  • Patent number: 6699470
    Abstract: A cell delivery device is prepared comprising a controllable degradable gel phase, meshed within a polymer substrate for use in tissue-engineering. The gel phase comprises a degradable, natural or synthetic polymer, and includes a suspension of living cells. The polymer substrate comprises a biocompatible, degradable polymer, and may be synthetic or natural. Degradation of the gel phase may be controlled by enzyme activity or adjustment of gel phase physical properties. In one embodiment, the gel phase contains an enzyme and/or enzyme inhibitor to control degradation of the gel phase. The device is useful in tissue replacement and repair, and more particularly, in the repair of cartilage tissue.
    Type: Grant
    Filed: October 10, 2000
    Date of Patent: March 2, 2004
    Assignee: Massachusetts Institute of Technology
    Inventors: Guillermo A. Ameer, Robert S. Langer, Jr.
  • Patent number: 6680184
    Abstract: A temperature-stable droplet is provided containing a temperature-stable hydrocolloid membrane. The hydrocolloid membrane encapsulates a liquid that contains at least one enzyme, a cell, a biological agent, a pharmaceutical agent, an immunological agent, or mixtures thereof, and at least one of a locust bean gum, a natural thickening agent, a guar, polyvinylpyrrolidone, Konjac mannan, methylcellulose, hydroxymethylcellulose, calcium gluconate, glucomannan, or mixtures thereof. Preferably, the hydrocolloid membrane comprises at least one of methoxy pectin, Konjac mannan, sodium alginate, or mixtures thereof, and at least one of a locust bean gum, methylcellulose, hydroxymethylcellulose, glucomannan, or mixtures thereof. The hydrocolloid membrane encapsulating the liquid is a thickness capable of holding the liquid without bursting through a temperature range of about −20° C. to about 90° C.
    Type: Grant
    Filed: September 29, 1999
    Date of Patent: January 20, 2004
    Assignee: Yissum Research & Development Co. of Hebrew University
    Inventor: Amos Nussinovitch
  • Patent number: 6649384
    Abstract: A method and system for the effective and consistent encapsulation of viable (i.e., living or physiologically active) biological material (preferably, pancreatic islets also known as islets of Langerhans) with a polymeric material (preferably, a biocompatible semipermeable alginate) to form a gelled capsule, which preferably can be transplanted into genetically dissimilar hosts. The method includes an electrostatic mixing process for producing encapsulated cell clusters with at least two polymeric coatings, and the system includes an improved spinning disk atomizer. In an embodiment, biological material is encapsulated in a first alginate layer, the resultant capsules are suspended in a liquid carrier medium such as a saline solution, an electrostatic charge is applied to the carrier medium which is then introduced into an alginate solution, and the resultant suspension is atomized and gelled to form a second alginate layer.
    Type: Grant
    Filed: July 5, 2001
    Date of Patent: November 18, 2003
    Assignee: Islet Technology, Inc.
    Inventors: Stephen E. Walsh, Monte R. Canfield, Nancy J. Drake
  • Patent number: 6641832
    Abstract: An angiogenic material is prepared which promotes extensive vascularization when implanted in animal tissue. The angiogenic material is preferably used in microcapsule coatings and microspheres for implantation in animals. In microcapsules, the angiogenic material promotes better exchange of nutrients, waste products and cellular products between encapsulated cells and the circulatory system of the host animal. Preferably, the angiogenic material consists of a biocompatible polymer and a vascularizing compound consisting of polymerizable compounds capable of forming anions. Microspheres containing the angiogenic material may be used to assist in recovery of ischemic heart muscle by injection of the microspheres into the heart muscle or blood vessels serving the ischemic area. Also disclosed is a method of forming small microcapsules and microspheres by passing cell aggregates or air bubbles through layers of a density gradient.
    Type: Grant
    Filed: December 20, 2000
    Date of Patent: November 4, 2003
    Inventors: Michael Vivian Sefton, Julia Elizabeth Babensee, Michael Humphrey May
  • Patent number: 6632446
    Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.
    Type: Grant
    Filed: October 23, 2000
    Date of Patent: October 14, 2003
    Assignee: The Board of Regents, University of Texas System
    Inventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
  • Patent number: 6627422
    Abstract: A device is provided containing cells or tissue distributed on a filamentous cell-supporting matrix which is encapsulated by a semi-permeable membrane which can be immunoisolatory. The matrix may be formed of a plurality of monofilaments twisted into yarn that is in non-woven strands, or of the monofilaments or yarn woven into a mesh. Configurations of the matrix include a hollow cylinder, tube, solid cylinder or cord. A coating of extracellular matrix molecules may be on the matrix, or the matrix may be treated with plasma irradiation to enhance cell adhesion. The device can be made by inserting the matrix in a hollow membrane tube, injecting cells or tissue into the tube and sealing ends of the tube. The device is particularly useful for implantation into a mammalian host to provide therapy resulting from a biologically active molecule produced by the cells and tissue.
    Type: Grant
    Filed: December 21, 2000
    Date of Patent: September 30, 2003
    Assignee: Neurotech S.A.
    Inventors: Rebecca Li, David Rhein
  • Patent number: 6616912
    Abstract: A bi-component microporous hollow fiber membrane structure is provided for in vivo propagation of cells and use in testing of the effect of medical treatments on cells within the structure. The structure has an inner structure fabricated from a first bio-compatible polymer and an outer structure fabricated from a different polymer that has a lower tendency for cell adhesion than the inner structure polymer. In this way, the inner structure can be selected to optimize cell propagation and the outer structure can be fabricated from a polymer which optimizes the removal of the bi-component structure from its implanted location. The inner and outer structures may have a pore size between 10 and 1000 Angstroms and 100 and 2000 Angstroms, respectively, and be formed from polysulfone or polyether sulfone and polyvinyledene difuoride, respectively. The membrane structure can form macrocapsules containing media and living cells for implanting.
    Type: Grant
    Filed: January 5, 2001
    Date of Patent: September 9, 2003
    Assignee: Spectrum Laboratories, Inc.
    Inventors: Roy T. Eddleman, Jesus Martinez
  • Patent number: 6592886
    Abstract: A stable cross-linked alginate gel such as in the form of alginate gel beads encapsulating transplant materials is produced by binding surplus multivalent cations remaining after cross-linking alginate with the cations. A cross-linked alginate gel containing the surplus cations is contacted with a solution of multivalent anions such as sodium sulfate solution to bind the surplus cations. Preferably, a dehydration preventing agent such as protein, bone powder or implant substances is present during cross-linking. A hydrophobic substance such as a perfluoro hydrocarbon or an emulsion may be present during cross-linking to fill spaces between alginate chains. Alginate gel beads produced by the process have long term stability after transplanting.
    Type: Grant
    Filed: January 27, 2000
    Date of Patent: July 15, 2003
    Assignee: CellMed AG
    Inventor: Ulrich Zimmermann
  • Patent number: 6582391
    Abstract: An implantable device having a body of matrix material made up of insoluble collagen fibrils, and disposed therewithin (a) a plurality of vertebrate cells; and (b) a plurality of microspheres each of which consists primarily of one or more of the following materials: collagen, polystyrene, dextran, polyacrylamide, cellulose, calcium alginate, latex, polysulfone, or glass.
    Type: Grant
    Filed: July 2, 2002
    Date of Patent: June 24, 2003
    Assignee: Transkaryotic Therapies, Inc.
    Inventor: Rochelle Mineau-Hanschke
  • Patent number: 6558665
    Abstract: Particles such as islet cells are encapsulated by a method that forms a coating of uniform thickness that conforms to the size and shape of the particles. Two substantially immiscible liquids of different densities are provided in a container as upper and lower liquids such that an interface exists between the liquids. The upper liquid is less dense and has a greater viscosity than the lower liquid which is a coating liquid containing particles to be encapsulated. A tube is positioned in the upper liquid such that an orifice of the tube is above the interface. A pump connected to the tube sucks liquid through the tube at a rate sufficient to form a spout containing substantially the lower liquid extending between the interface and the tube orifice. The spout has maximum diameter at the interface and decreases in diameter as the spout approaches the tube orifice.
    Type: Grant
    Filed: May 18, 2000
    Date of Patent: May 6, 2003
    Assignee: Arch Development Corporation
    Inventors: Itai Cohen, Sidney Nagel, Horacio Rilo, Milan Mrksich
  • Patent number: 6544762
    Abstract: Tissue-equivalent and biopolymer tubes and rods include fibrils which are oriented (aligned) by a magnetic field. These oriented fibrils provide enhanced mechanical and cell guidance properties to the tissue-equivalent and biopolymer tubes. One such tissue-equivalent tube includes a body of collagen gel with mammalian tissue cells interspersed therein. The collagen fibrils are circumferentially oriented within the tubular body by a magnetic field, thereby inducing circumferential orientation of the cells. One such biopolymer rod includes collagen fibrils longitudinally oriented along the rod axis by a magnetic field that guides invasion of cells. Methods of making magnetically oriented tissue-equivalent and biopolymer tubes and rods are also disclosed.
    Type: Grant
    Filed: October 10, 2000
    Date of Patent: April 8, 2003
    Assignee: Regents of the University of Minnesota
    Inventors: Robert T. Tranquillo, Stefano Guido
  • Publication number: 20020192190
    Abstract: A method of creating tolerance to transplanted cells, tissue, or organs without the need for continuous immunosuppression. A tolerizing dose of a cell or tissue within a membrane structure is implanted into a patient. Once the patient becomes tolerant to the cell or tissue, a tissue or organ is implanted which will no longer be recognized as foreign matter. The method makes animal organs practical for human use, prevents autoimmune destruction as well as immune rejection. It has applications in treatment and prevention of many mammalian diseases.
    Type: Application
    Filed: January 7, 1999
    Publication date: December 19, 2002
    Inventor: PAUL P. LATTA
  • Patent number: 6479066
    Abstract: A device and method of using the device are provided for implanting cell cultures in a host. The device is formed of a deformable body, a microporous membrane and a sealable port. The shape of the body which is preferably rounded can be altered by applying stress or pressure, The body comprises a continuous wall constructed of a mesh material, and the membrane lines a surface of the body. The wall and membrane define an enclosed three-dimensional cavity for containing a cell culture. Openings of the membrane allow for passage of therapeutic substances produced by the cells and nutrients or biomolecules produced by host. The sealable port is configured for adding a cell culture to the cavity, and is formed of a material that is capable of resealing after being punctured with a needle. Because the device is deformable, it can be compressed and placed in an implantation site where it expands to conform to contours of tissue surrounding the site.
    Type: Grant
    Filed: December 16, 1999
    Date of Patent: November 12, 2002
    Assignee: RST Implanted Cell Technology, LLC
    Inventor: Stanley D. Harpstead
  • Patent number: 6465226
    Abstract: Biologically active substances such as cells or tissue are microencapsulated by methods that provide a high proportion of microcapsules containing a core of the biologically active substance as compared to microcapsules not containing the biologically active substance. Microcapsules are obtained having a maximum diameter of 300 micrometers and a high concentration of biologically active substance. A solution of encapsulating material such as alginate containing dispersed biologically active substance is passed through an inner channel of a two-channel spray nozzle to form droplets containing a core of the biologically active substance. Air flow from an outer channel of the nozzle causes the droplets to break off from the nozzle. Conditions of air flow and flow rate of solution are selected to obtain droplets having a volume of 1.5 to 4 times the volume of the biologically active substance that forms the core.
    Type: Grant
    Filed: October 19, 1998
    Date of Patent: October 15, 2002
    Inventor: Ulrich Zimmermann
  • Patent number: 6465001
    Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules. A medical condition at a localized site is treated by applying a polymerization initiator and then applying a substantially water-soluble, degradable macromer of at least 200 mw and having at least two crosslinkable substituents, and polymerizing the macromer to form a crosslinked polymeric material at the site.
    Type: Grant
    Filed: March 3, 1998
    Date of Patent: October 15, 2002
    Assignee: Board of Regents, The University of Texas Systems
    Inventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet Sawhney, Neil Desai, Syed Hossainy, Jennifer L. Hill-West
  • Patent number: 6464998
    Abstract: The present invention provides cell compositions for in vivo implantation, and designed for the sustained and controlled delivery of therapeutic substances.
    Type: Grant
    Filed: July 11, 1996
    Date of Patent: October 15, 2002
    Assignee: Aventis Pharma S.A.
    Inventors: Yves Beuzard, Olivier Danos, Vincent Descamps, Jean-Michel Heard, Philippe Moullier, Nadia Naffakh, Michel Perricaudet, William Vainchenker
  • Patent number: 6426214
    Abstract: Cell encapsulating devices capable of maintaining large numbers of viable cells are provided containing an inert, substantially cell-free core that displaces cells, a permeable membrane and a zone for maintaining cells. The permeable membrane surrounds the core such that the zone of cells is bounded by the core and the permeable membrane. A preferred device contains a polytetrafluoroethylene permeable membrane and a flexible polymer core having a plurality of ridges and valleys running lengthwise along the core. The cell zone may contain support means for cell attachment and the core may have an outer boundary containing a material that promotes cell adhesion. Preferably, the cell zone has a thickness such that at least about 10% of the cells, more preferably at least about 50% or 80%, in a cell layer located closest to the outer boundary of the core remain viable. The thickness is preferably less than 500 microns such as 25 to 250 microns or 50 to 100 microns.
    Type: Grant
    Filed: November 8, 1999
    Date of Patent: July 30, 2002
    Assignee: Gore Enterprise Holdings, Inc.
    Inventors: Mark D. Butler, Stanley L. Mish
  • Patent number: 6419920
    Abstract: A composition having a body of matrix material made up of insoluble collagen fibrils, and disposed therewithin (a) a plurality of vertebrate cells; (b) a plurality of microspheres; and (c) an agent such as a factor that promotes vascularization, a cytokine, a growth factor, or ascorbic acid.
    Type: Grant
    Filed: October 5, 1999
    Date of Patent: July 16, 2002
    Assignee: Trans Karyotic Therapies, Inc.
    Inventor: Rochelle Mineau-Hanschke
  • Patent number: 6399341
    Abstract: An artificial pancreas is described herein which comprises one or more viable and physiologically active pancreatic islet cells capable of producing insulin, encapsulated within a semipermeable spheroidal membrane comprising agar gel. Further disclosed are a method for producing agar microbeads, a tissue implantation method and a reseeding method for the artificial pancreas.
    Type: Grant
    Filed: November 2, 1999
    Date of Patent: June 4, 2002
    Inventors: Jan Philip Stegemann, John Joseph O'Neil, Claudy Jean Paul Mullon
  • Patent number: 6372501
    Abstract: The present invention provides an immortalized insulin producing human &bgr;-cell which may be rendered glucose responsive by suitable bioengineering methods. The invention also provides a method for producing an immortalized glucose responsive insulin producing human &bgr;-cell comprising the steps of selecting an unregulated immortalized human insulin secreting &bgr;-cell, transecting said selected cell line with elements for the genetic control of glucose responsiveness and proliferating said transfected &bgr;-cell accordingly.
    Type: Grant
    Filed: May 4, 2000
    Date of Patent: April 16, 2002
    Assignees: Aberdeen University, The University of Sheffield, The University of Leicester, University College London
    Inventors: Albert Aynsley-Green, Keith Lindley, Kevin Docherty, Mark Dunne, Wendy MacFarlane, Roger Frank Lever James
  • Patent number: 6368592
    Abstract: Oxygen is supplied to cells in vitro or in vivo by generating oxygen with an oxygen generator that electrolyzes water to oxygen and hydrogen. Oxygen can be generated substantially without generating free hydrogen using a multilayer electrolyzer sheet having a proton exchange membrane sandwiched by an anode layer and a cathode layer. The oxygen generator may be used to supply oxygen to cells contained by a culture plate, a culture flask, a microtiter plate or an extracorporeal circuit, or to cells in an encapsulating chamber for implanting in the body such as an immunoisolation chamber bounded by a semipermeable barrier layer that allows selected components to enter and leave the chamber. A bioactive molecule may be present with the cells.
    Type: Grant
    Filed: July 16, 1999
    Date of Patent: April 9, 2002
    Assignee: Massachusetts Institute of Technology
    Inventors: Clark K. Colton, Larry L. Swette
  • Patent number: 6368858
    Abstract: Cells in a matrix or in the matrix in a vessel are grown to form a multicellular aggregate. Pressure is exerted on the growing cells by the matrix or the matrix together with the vessel due to growing cellular mass displacing the matrix. A value representing pressure exerted on the cells is calculated and the pressure is modulated to control growth of the multicellular aggregate, or to produce a multicellular aggregate of a pre-selected size or a pre-selected size and shape. Matrices include agarose, alginate and collagen gels, and the pressure exerted on the cells can be non-isotropic. The cells may be tumor cells, or liver, pancreatic, brain, skin, bone or muscle cells, and cell growth can be in vitro or in vivo. When collagen forms the matrix, the matrix may contain glycosaminoglycan.
    Type: Grant
    Filed: July 22, 1998
    Date of Patent: April 9, 2002
    Assignee: The General Hospital Corporation
    Inventors: Gabriel Helmlinger, Paolo A. Netti, Robert J. Melder, Rakesh K. Jain, Hera Lichtenbeld-Dubois
  • Patent number: 6365385
    Abstract: Cells, preferably isolated pancreatic islet cells, are treated with a compound or a combination of compounds selected from an antioxidant, an anti-cytokine, an anti-endotoxin and an antibiotic. The compound or combination of compounds is in a medium for culturing the cells before microencapsulation, in a medium for cryopreserving the cells by freezing followed by thawing and microencapsulation, in a medium for culturing the cells after microencapsulation, or in a medium for culturing the cells before microencapsulation and in a medium for culturing the cells after microencapsulation. Microcapsules containing cells may be incubated with a physiologically acceptable salt to increase durability of the microcapsules. In a preferred method, isolated pancreatic islet cells are cultured for about 12 to about 36 hours in a medium containing an antioxidant as the compound, cryopreserved by freezing in a medium containing the compound or combination of compounds, thawed and microencapsulated.
    Type: Grant
    Filed: December 1, 1999
    Date of Patent: April 2, 2002
    Assignee: Duke University
    Inventor: Emmanuel C. Opara
  • Patent number: 6352707
    Abstract: Immune recognition of a transplant such as tissue implanted in a host mammal is obscured by encapsulating the transplant in a hydrogel matrix containing gelatin, dextran, at least one nitric oxide inhibitor and polar amino acids. The polar amino acids increase rigidity of the matrix and allow direct injection of the encapsulated transplant into a mammal without further immunosuppression. Preferably, the nitric oxide inhibitor is a combination of L-cysteine and an L-arginine analogue such as aminoguanidine, and the polar amino acids are a combination of L-glutamic acid, L-lysine and L-arginine. The matrix may also contain a superoxide inhibitor such as EDTA. Implanting can be carried out by applying a buffer medium containing a nitric oxide inhibitor to an implant site, implanting the encapsulated transplant, and applying to the implant site a buffer medium which may contain a nitric oxide inhibitor. The buffer medium may also contain a superoxide inhibitor.
    Type: Grant
    Filed: July 1, 1999
    Date of Patent: March 5, 2002
    Inventor: Anton-Lewis Usala
  • Patent number: 6312942
    Abstract: Substances such as chemical substances and biological substances including animal, vegetable and microbial cells are encapsulated using a process and an apparatus wherein a coil through which alternating current flows causes a magnet to vibrate creating vibrations such as in the range of between 300 to 4000 Hz that are transmitted to an encapsulating fluid containing the substance to form small substantially spherical particles containing the substance. The apparatus includes a pulsation chamber containing a movable wall for receiving the encapsulating fluid containing the substance to be encapsulated. A nozzle is spaced downstream from the pulsation chamber for receiving the encapsulating fluid from the pulsation chamber. A permanent magnet is mounted on the movable wall, and a coil is spaced from the permanent magnet by an air gap and is located proximate to the permanent magnet.
    Type: Grant
    Filed: November 23, 1998
    Date of Patent: November 6, 2001
    Assignee: Inotech AG
    Inventors: Raphael Plüss-Wenzinger, Fritz Widmer, Christoph Heinzen, Harry Brandenberger
  • Patent number: 6303136
    Abstract: A device is prepared having cells or tissue attached to a non-degradable filamentous matrix surrounded by a semi-permeable membrane. The matrix is preferably formed of a plurality of monofilaments twisted into a yarn or woven into a mesh, and can be in the form of a cylinder. When implanting the device, the semi-permeable membrane is preferably immunolsolatory, and the cells or tissue may produce a biologically active molecule to provide therapy. To enhance cell or tissue adhesion, the matrix is coated with extracellular matrix molecules or treated to provide a surface charge. The device can be made by inserting the matrix into a capsule formed of the semi-permeable membrane, distributing the cells or tissue on the matrix through an opening of the capsule, and sealing the opening of the capsule.
    Type: Grant
    Filed: April 12, 1999
    Date of Patent: October 16, 2001
    Assignee: Neurotech S.A.
    Inventors: Rebecca Li, David Rein
  • Patent number: RE38027
    Abstract: Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.
    Type: Grant
    Filed: June 30, 1999
    Date of Patent: March 11, 2003
    Assignee: The Rogosin Institute
    Inventors: Kanti Jain, Albert L. Rubin, Barry Smith