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WO1991000119A1 - Dispositif implantable - Google Patents

Dispositif implantable Download PDF

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Publication number
WO1991000119A1
WO1991000119A1 PCT/AU1990/000281 AU9000281W WO9100119A1 WO 1991000119 A1 WO1991000119 A1 WO 1991000119A1 AU 9000281 W AU9000281 W AU 9000281W WO 9100119 A1 WO9100119 A1 WO 9100119A1
Authority
WO
WIPO (PCT)
Prior art keywords
animal
cells
tube
tubes
conditions
Prior art date
Application number
PCT/AU1990/000281
Other languages
English (en)
Inventor
Thomas Eli Mandel
Brett Charlton
John Edward Moran
Thomas Loudovaris
Original Assignee
Baxter International Inc.
The Walter And Eliza Hall Institute Of Medical Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Baxter International Inc., The Walter And Eliza Hall Institute Of Medical Research filed Critical Baxter International Inc.
Publication of WO1991000119A1 publication Critical patent/WO1991000119A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/022—Artificial gland structures using bioreactors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

Definitions

  • the present invention relates to an i plantable device for keeping transplanted cells alive in vivo, and to methods of implanting such a device, whereby vascularisation of the exterior of the device is achieved in vivo, before or after instilment of the living cells into the device.
  • the invention also relates to methods of treating animals comprising implantation of the device containing selected cells, or the subsequent instilment of selected cells into the empty device after vascularisation has occurred.
  • Endocrine deficiency diseases are currently treated with hormone replacement therapy.
  • the therapeutic regimens employed range from multiple daily injections or oral therapy to implants that provide a steady hormone level over months. While this mode of therapy maintains an improved quality of life over the untreated disease state, it is not equivalent to the normal state where an organ maintains relative homeostasis in the individual by supplying a hormone in response to a sensed, variable metabolic need.
  • Current inability to produce artificial infusion devices that can mimic normal endocrine organ function has motivated research efforts to transplant endocrine organs or their essential cellular elements into deficient individuals.
  • Intrasolation surrounds the transplanted organ, or its essential elements, with a physical barrier that is impermeable to the active molecules and cells of the immune system, but is permeable to nutrients, the hormone(s) secreted by that organ, and the metabolite(s) that trigger the release of the hormone(s).
  • Extant immunoisol tion devices can be divided Into vascular and extravascular types.
  • Vascular devices generally contain endocrine cells in a chamber surrounding artificial blood vessels, wherein the vessel walls serve both as an immune barrier and as an extension of the circulatory system.
  • vascular devices 1 The advantage of vascular devices 1s the proximity of the endocrine cells to the blood, which permits adequate access to nutrients and oxygen, and shortens the time for the cells to receive a metabolic stimulus and deliver the hormone response into the circulation.
  • vascular devices have been unsuccessful because blood clotting could not be prevented on the blood contacting surfaces.
  • Extravascul r devices contain endocrine cells in a chamber bounded by an Immune barrier membrane.
  • the cells depend on molecules diffusing from adjacent blood vessels through tissues, body fluids and the limiting membrane to supply their nutrients and oxygen, and to sense the concentration of the metabolites that trigger their secretory response. In turn the secreted hormone must diffuse back through the limiting membrane, body tissues and then body fluids to reach the circulatory system.
  • islets of Langerhans the active elements of the endocrine pancreas, average about 150 micrometers in diameter and typically contain 3 - 5,000 cells, and are intensely vascularised such that any cell 1s within 2 cell diameters from a capillary. It follows, that an artificial device containing Intact islets, even when the surface of each islet is closely Invested by a capillary network, does not provide as short a diffusion path as the native islet environment.
  • Extravascular devices are also thought to have failed because their surface initiated a foreign body response by the surrounding tissue.
  • Foreign body responses typically establish a thick and dense fibrous capsule, relatively devoid of blood vessels, around the implanted material. This capsule is thought to seriously retard diffusion of essential nutrients, metabolites and hormones between the device and blood vessels, whether by distance effects or by diffusive resistance of the fibrous capsule.
  • the establishment of this fibrous capsule is causally related to recognition of the foreign implant by macrophages. Stimulated macrophages attempt to digest the surface of the implant by releasing enzymes and toxins at Its surface. It 1s believed to be advantageous for endocrine cells within the Implant to avoid the release of such toxic material in their near vicinity, since they may also be damaged by these agents.
  • Another object of the invention is to provide methods of treating disorders such as endocrine hormone deficiency states in an animal.
  • the present invention derives from the entirely unexpected finding that living cells may be transplanted into the body and maintained in a functionally viable state in an implantable device according to the invention.
  • the empty device is initially implanted in an animal and left to allow vascularisation of the exterior of the device to occur. A substantial number of viable cells can then be instilled into the device in vivo some time after original implantation of the device, without contamination of the instilled cells.
  • the device may be pre-filled with selected viable cells prior to implantation. In either case the cells may later be emptied and the device replenished in situ.
  • the size and integrity of the device allows it to be stably located in the body by a surgeon and be maintained as a recoverable entity.
  • an implantable device for keeping transplanted cells alive in vivo, in an animal comprising: at least one thin walled, hollow, cell closeable, semi-permeable tube having: an Internal diameter appropriate to enable cells within the tube to remain functionally viable; and a large pore hydrophobic membrane wall of appropriate thickness, inducing vascularisation on Implanting thereby permitting nutrient and metabolite transfer between body fluids surrounding the tube and the cells, providing an immune barrier between the cells and the body fluids, and enabling the cells within the tube to remain viable.
  • the length of the tubes will vary according to their other dimensions such as wall thickness and Internal diameter and also according to the cell type and implantation site within the body.
  • tubes of about 30cm in length are employed.
  • the device may further comprise means to close the tube, which may be 1n the form of a plug, a cap, a clamp or the like.
  • an Implantable device for keeping transplanted cells alive in vivo.
  • an animal comprising: a plurality of thin walled, hollow, cell closeable, semi-permeable tubes, each tube having a first and a second end and having: an internal diameter appropriate to enable cells within the tube to remain functionally viable; a large pore hydrophobic membrane wall of appropriate thickness, inducing vascularisation on implanting thereby permitting nutrient and metabolite transfer between body fluids surrounding the tube and the cells, providing an immune barrier between the cells and the body fluids, and enabling the cells within the tube to remain viable; a first support operatively associated with the first ends of said tubes having a closeable entrance; a second support operatively associated with the second ends of said tubes having a closeable exit; the closeable entrance and exit permitting filling of the tubes with selected viable cells.
  • This form of the invention generally includes means to close the entrance and exit which typically are in the form of first and second closure caps for closing the entrance and exit respectively.
  • the length and number of the tubes will vary according to the volume of cells required, and other factors such as implantation site and access to the systemic circulation. Generally 3 to 12 tubes are present, the length of the tubes varying between about 3 to about 30 cm. Advantageously 4 or 5 tubes of approximately 10cm in length are employed.
  • the first and second ends of the tubes may be manifolded so as to communicate with the respective exit and entrance of the device.
  • the entrance and exit may communicate with chambers inside the first and second supports respectively which in turn communicate with the first and second ends of the tubes.
  • the tubes are drawn together at the first and second ends to fit within the entrance and exit respectively.
  • an Implantable device for keeping transplanted cells alive 1n vivo. 1n an animal, comprising: a plurality of thin walled, hollow, cell closeable, semi-permeable tubes, each tube having a first and a second end and having: an internal diameter appropriate to enable cells within the tube to remain functionally viable; a large pore hydrophobic membrane wall of appropriate thickness, inducing vascularisation on implanting thereby permitting nutrient and metabolite transfer between body fluids surrounding the tube and the cells, providing an immune barrier between the cells and the body fluids, and enabling the cells within the tube to remain viable; the first ends of said tubes communicating with a closeable entrance thereby permitting filling and closure of the tubes; and a support operatively associated with the tubes, for holding at least a portion of the tubes in proximal relationship with each other.
  • the components of the device are constructed of, or are coated with, bio-compatible materials such as medical implant grade silicone rubber, polyethylene, polypropylene, cuprophane, polyacrylonitrile or teflon to protect against a foreign body response being mounted against the implant.
  • bio-compatible materials such as medical implant grade silicone rubber, polyethylene, polypropylene, cuprophane, polyacrylonitrile or teflon to protect against a foreign body response being mounted against the implant.
  • small diameter thin walled hollow-tubes are used to provide shorter diffusion paths between the blood vessels outside the wall and all the cells inside the tube.
  • the hollow tubes are constructed of a large pore hydrophobic semi- permeable material, which is capable of encapsulating the living cells and of inducing vascularisation to occur about the tube on implanting in the body of any animal.
  • Suitable materials therefore are those having a pore-size generally greater than about 150,000 daltons, ( i.e. greater than about 0.005 ⁇ m), such as appropriate grades of polyethylene, polypropylene or polyacrylonitrile. Goretex (Registered Trade Mark) may also be used.
  • the pore size of the material is 1n the range of about 0.005 ⁇ m to 1.0 ⁇ m, typically from about 0.05 ⁇ m to about 0.6 ⁇ m with a pore size of 0.5 ⁇ m being desirable.
  • the lower limit of pore size is related to the dimension of wall thickness 1n that the thinner the wall of the tube, the smaller the pore size can be.
  • pore sizes less than 150,000 daltons should be achievable with tubes having appropriately thin walls.
  • the upper limit of pore dimensions should be less than those which permit transfer of undesirable contaminants from the blood Into the tube. The bi ⁇ compatibility of the material from which the tube Is made is also a factor.
  • the tubes may be coated with biocompatlbllity-enhancing substances such as fibronectln, laminin, or collagen, and/or be coated with a biodegradable gel containing corticosterolds or other drugs that regulate the formation of flbrotlc tissue around the device.
  • biocompatlbllity-enhancing substances such as fibronectln, laminin, or collagen
  • the internal dimensions of a tube should be no greater than those which permit adequate nutrient transfer between blood capillaries surrounding the tube and cells within the tube so that the cells remain viable in vjvp.
  • the wall thickness of the tubes 1s less than about lOO ⁇ m, typically from about 45 ⁇ m to about 95 ⁇ m, and their internal diameter 1s generally from about 20 ⁇ m to 1 mm, typically from about 200 ⁇ m to about 500 ⁇ m.
  • the support(s) will be in the form of a block of silicone rubber or other suitable material into which the tubes are embedded.
  • the support may comprise any appropriate means of holding the tubes together such as a band or ligature or a suitable housing.
  • tubes on implantation in the body are closed to the entry of external cells at both ends by means of a cap, plug, or filter, or other suitable closure means, which are removable to allow Instilment of cells.
  • a method of Implanting a device of the first embodiment 1n an animal comprising: implanting the device in the animal under aseptic conditions, with the tube of the device closed to intrusion by external cells; leaving the device in the animal whereby vascularisation occurs about the tube; filling the tube of the Implanted device under aseptic conditions with selected viable cells ; and closing the tube of the implanted device under aseptic conditions.
  • a method of implanting a device of the first embodiment, in an animal comprising: filling the tube of the device with selected viable cells under aseptic conditions; closing the tube under aseptic conditions; implanting the device in an animal under aseptic conditions; and leaving the implanted device in the animal whereby vascularisation occurs about the tube.
  • a method of implanting a device of the second or third embodiment in an animal comprising: filling the tubes of the device with selected viable cells under asceptic conditions; closing the tubes under asceptic conditions; implanting the device 1n an animal under asceptic conditions; and leaving the Implanted device in the animal whereby vascularisation occurs about the tubes.
  • the implanted device may be emptied and refilled with cells.
  • the exit of the device may be adapted to attach to a vacuum pump so that on attachment of the device to the pump a vacuum 1s created inside the tube to facilitate filling of the tube with the selected cells.
  • the pressure inside the tube being controlled by means of a valve connected with the pump.
  • the device is implanted into highly vascularised host tissue e.g., a surgically-formed pouch (fold) in the omentum or into subcutaneous or other adipose tissue. It is anticipated that the device may also be implanted and/or filled percutaneously under radiological control or other means, or that one end of a tube of the device can be left in communication with the external surface of the animal's body and be filled externally without the need for further invasive procedures.
  • highly vascularised host tissue e.g., a surgically-formed pouch (fold) in the omentum or into subcutaneous or other adipose tissue.
  • the device may also be implanted and/or filled percutaneously under radiological control or other means, or that one end of a tube of the device can be left in communication with the external surface of the animal's body and be filled externally without the need for further invasive procedures.
  • the exterior of the hollow tubes may be coated with anglogenic factors, or a biodegradable gel containing anglogenic factors, which are capable of enhancing capillary growth proximate to the external surface of the tubes.
  • Suitable anglogenic factors include slow release heparin, platelet derived growth factor, epidermal growth factor, or cis-hydroxyproline.
  • a method of providing an animal with transplanted viable cells in vivo which secrete a substance required by the animal comprises:
  • a ninth embodiment of the invention there is provided a method of providing an animal with transplanted viable cells in vivo which secrete a substance required by the animal, which method comprises: implanting a device according to the second or third embodiment into the animal in accordance with the method of the fifth or seventh embodiment; and wherein the tubes are filled with a quantity of cells which secrete an effective amount of the substance.
  • the invention provides a method of treating an animal with an endocrine hormone deficiency state, wherein the selected cells are capable of producing at least one appropriate endocrine hormone.
  • pancreatic deficiency states such as deficiency of the pancreatic hormone Insulin 1n Diabetes Mellitus.
  • the treatment of deficiency states due to the absence or failure of other endocrine organs such as the thyroid, adrenals, pituitary, ovaries or testes, 1s also within the scope of the present invention.
  • a deficiency state involves more than one hormone such as in generalised pituitary failure
  • 1 is possible to Instill more than one cell type producing the appropriate hormone into an Individual tube or alternatively different cell types may be Inserted into different tubes In the same device or Into separate devices, for implantation in the animal.
  • the effective number of cells of a selected cell type required will obviously vary according to the particular deficiency state and its severity, and according to the age, sex, weight, general condition, etc of the patient and other variables affecting the clinical state such as intercurrent illnesses.
  • the site of implantation in the body will also Influence the number of cells required, due to factors such as distance from target organ and degree of access to the systemic circulation.
  • a method of providing an animal with transplanted viable cells in vivo which metabolise a substance in the animal comprises: implanting a device according to the first embodiment into the animal in accordance with the method of the fourth or sixth embodiment; and wherein the tube is filled with a quantity of selected viable cells which metabolise an effective amount of the substance.
  • a method of providing an animal with transplanted viable cells in vivo which metabolise a substance in the animal comprises: implanting a device according to the second or third embodiment Into the animal in accordance with the method of the fifth or seventh embodiment, and wherein the tubes are filled with a quantity of selected viable cells which metabolise an effective amount of the substance.
  • Substances to be metabolised include metabolites or waste products produced by the animal, or externally derived toxins, which the animal Is incapable of dealing with effectively itself, and which would be harmful to the animal 1f allowed to accumulate.
  • the invention also includes within its scope methods of sensing the presence of, or monitoring the concentration of, compounds or elements within the body of an an animal. Such methods may be used in the diagnosis or monitoring of disease or deficiency states.
  • the selected cells implanted according to the Invention are capable of responding to or reacting with an appropriate compound, element, or condition and of producing a detectable entity.
  • the compound or element may be a hormone, an enzyme, an enzyme cofactor, an antigen, an antibody, a metabolite, a toxin, a vitamin, a protein, a trace element, and a gas, for example.
  • the detectable entity may be a metabolic product detectable in the blood or urine, or an alteration 1n celV membrane potential, detected by suitable sensing means.
  • the signal may be quantitatively measured where the compound or element 1s being monitored over a given time period.
  • the methods of the Invention are applicable to all animals, and are especially useful 1n the treatment of humans and mammals generally.
  • the cells used 1n the practice of the Invention are typically taken from an animal of the same species as the recipient, or of a different species, or the cells may be obtained from special cell lines or from tissue culture. Alternatively it would be possible to use autologous cells, which have been taken from the recipient animal and stored under appropriate conditions, and/or cultured in v1tro t before reimplantatlon according to the invention.
  • the device according to the invention overcomes many of the enumerated problems of prior art devices.
  • materials with large pore size were avoided since it was thought prior to the present invention that such materials would allow the entry of antibodies into the interior of the device resulting in destruction of the cells.
  • the inventors have found a number of advantages in using a large pore size membrane, namely: that large pore size membranes are easier to fabricate, they allow easier passage of large molecular weight nutrients (e.g. large fatty adds) from the blood stream to the Implanted cells and also they may be less effected by clogging with protein and other body substances.
  • the present device is the first device that both contains enough viable cells to be effective and more significantly allows a mechanism for Instilling cells Into the tubes some time after implantation and after vascularised tissue has grown around the tubes.
  • the shape of the present device allows for firm anchorage both by the surgeon being able to suture the semi-rigid ends to host tissue as well as through the device obtaining firm anchorage through tissue ingrowth around and between the multiple hollow fibres. This has not been achieved with previous devices which have just used isolated hollow fibres. Also, the single Integrated entity structure allows easy location and removal of the device 1f there are problems. This is much harder with single hollow fibres and impossible with implanted islet mlcrocapsule systems.
  • a tube of the device acts as an immune barrier that allows free passage of essential nutrients, oxygen and the secreted hormones, but is impermeable to active elements of the immune system.
  • the thickness of a tube of the device in effect minimizes the distance between any one cell contained inside the barrier and adjacent blood capillaries outside the barrier.
  • the device is capable of causing blood capillaries to form and remain near the surface of the immune barrier prior to, or after, instilment of cells inside the device. 4.
  • the device avoids establishment of a thick, dense fibrous capsule relatively devoid of blood vessels at the surface of the implant.
  • Figure 1 illustrates a schematic top plan view of a device of the invention.
  • Figure 2 illustrates a schematic top plan view of an alternative device of the invention.
  • the Figures illustrate preferred embodiments of the device according to the invention. Although 6 tubes are shown for the purpose of Illustration the number of tubes can be varied as required as may the length of the tubes.
  • Device 10 consists of multiple hollow tubes 1 having first ends 2 and second ends 3.
  • First ends 2 of hollow tubes 1 are operatively associated with first support 4.
  • First support 4 has a closeable entrance 5 for filling tubes 1 with cells, Into which first ends 2 of tubes 1 are Inserted. Entrance 5 1s reduced 1n size to fit a standard Record lock syringe.
  • Second ends 3 of tubes 1 are operatively associated with second support 7.
  • Second support 7 has a closeable exit 8, into which second ends 3 of tubes 1 are inserted, permitting the filling of tubes 1 with cells via entrance 5.
  • Hollow tubes 1 are composed of a polyethylene or polypropylene semi-permeable membrane material that elicits minimal foreign body response in the host and resists build-up of flbrotlc tissue on the exterior surface, with a pore size of about 0.5 ⁇ m, wall thickness of about 90 ⁇ m and internal diameter about 330 ⁇ m.
  • First support 4 and second support 7 may be composed of any appropriate potting substance such as epoxy resin, which may then be coated with a more biocompatible substance such as medical implant grade silicone rubber to render it more inert.
  • Entrance 5 and exit 8 at each extremity of device 10 have removable caps 9, caps 9 being constructed of or coated with a biocompatible substance such as silicone rubber.
  • Implantation of device 10 is a two-stage procedure carried out under strict aseptic conditions.
  • the first stage is to implant empty device 10, which may or may not be pretreated, externally and/or internally with biocompatibility-enhanclng factors such as fibronectin, and/or externally with angiogenic factors such as slow release heparin, Into subcutaneous tissue of the recipient.
  • biocompatibility-enhanclng factors such as fibronectin
  • angiogenic factors such as slow release heparin
  • exit 8 may be connected to vacuum pump 11 by means of conduit 12.
  • vacuum pump 11 On operation of vacuum pump 11 a vacuum 1s created in hollow tubes 1 prior to loading with selected cells via entrance 5.
  • the pressure 1n hollow tubes 1 is controlled by valve 13 connected to vacuum pump 11.
  • Caps 9 are then reinserted either as a friction fit or with the aid of a sealant or glue.
  • the selected cells are Isolated from suitable tissue by enzymatic digestion and purification procedures known In the art, to obtain as pure a cell preparation as possible, free from unwanted cells and other contaminants.
  • implantation of device 10 is carried out in a single step under strict aseptic conditions. This involves carefully removing both of caps 9 from entrance 5 and exit 8, of device 10 and aseptically loading hollow tubes 1 of device 10 with selected cells via entrance 5, by means of a standard Record lock syringe.
  • the selected cells are isolated from suitable tissue by enzymatic digestion and purification procedures known 1n the art, to obtain as pure a cell preparation as possible, free from unwanted cells and other contaminants.
  • exit 8 may be connected to vacuum pump 11 by means of conduit 12. On operation of vacuum pump 11 a vacuum is created in hollow tubes 1 prior to loading with selected cells via entrance 5. The pressure 1n hollow tubes 1 is controlled by valve 13 connected to vacuum pump 11.
  • Caps 9 are then reinserted either as a friction fit or with the aid of a sealant or glue.
  • the filled device 10 which may or may not be pretreated, externally and/or internally with biocompatibility-enhanclng factors such as fibronectin, and/or externally with angiogenic factors such as slow release heparin, is then aseptlcally implanted into subcutaneous tissue of the recipient. Vascular and connective tissue then grow around device 10, to supply the cells with essential nutrients.
  • the device of the present Invention will find wide application in the medical and veterinary fields.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nanotechnology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

L'invention se rapporte à un dispositif implantable servant à maintenir des cellules transplantées vivantes in vivo, dans le corps d'un animal. Le dispositif comprend: au moins un tube creux obturable à paroi mince, qui contient les cellules et qui présente un diamètre intérieur approprié, de façon à permettre aux cellules contenues dans le tube de rester fonctionnellement viables; ainsi qu'une paroi à membrane hydrophobe à larges pores et d'épaisseur appropriée, qui induit une vascularisation lors de l'implantation, pour permettre le transfert des substances nutritives et des métabolites entre les fluides corporels entourant le tube et les cellules, de façon à former une barrière immunitaire entre les cellules et les fluides corporels, et qui permet ainsi aux cellules contenues dans le tube de rester viables. Sont également décrits des procédés d'implantation du dispositif, grâce auxquels la vascularisation de l'extérieur du dispositif est assurée in vivo avant ou après l'instillation des cellules viables dans le dispositif. Le dispositif implanté peut être utilisé pour fournir à des animaux des cellules viables transplantées in vivo, qui sécrètent une substance requise par l'animal ou qui effectuent le métabolisme d'une substance dans le corps de l'animal.
PCT/AU1990/000281 1989-06-30 1990-07-02 Dispositif implantable WO1991000119A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPJ498389 1989-06-30
AUPJ4983 1989-06-30

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WO1991000119A1 true WO1991000119A1 (fr) 1991-01-10

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Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992009311A1 (fr) * 1990-11-29 1992-06-11 Bioricerche S.N.C. Di Carla Zedda Prothese vasculaire a double paroi synthetique et biocompatible contenant des cellules a secretion d'hormone
WO1993000127A1 (fr) * 1991-06-28 1993-01-07 Brown University Research Foundation Systeme d'implant nerveux
WO1993002635A1 (fr) * 1991-07-30 1993-02-18 Baxter International Inc. Implant foramine
WO1993021902A1 (fr) * 1992-04-24 1993-11-11 Somatix Therapy Corporation Dispositif implantable therapeutique et biocompatible
WO1994001166A1 (fr) * 1992-07-13 1994-01-20 Brown University Research Foundation Dispositifs implantables pour la liberation de composes neuro-inhibiteurs
US5314471A (en) * 1991-07-24 1994-05-24 Baxter International Inc. Tissue inplant systems and methods for sustaining viable high cell densities within a host
WO1994018906A1 (fr) * 1993-02-18 1994-09-01 New England Deaconess Hospital, Corp. Organe artificiel implantable
US5344454A (en) * 1991-07-24 1994-09-06 Baxter International Inc. Closed porous chambers for implanting tissue in a host
JPH08500255A (ja) * 1992-04-01 1996-01-16 バクスター・インターナショナル・インコーポレーテッド 血管形成組織移植システムおよびその方法
US5487739A (en) * 1987-11-17 1996-01-30 Brown University Research Foundation Implantable therapy systems and methods
JPH08502667A (ja) * 1992-07-30 1996-03-26 ザ・ユニバーシティ・オブ・トリド 生体人工膵臓
US5554148A (en) * 1987-11-17 1996-09-10 Brown University Research Foundation Renewable neural implant device and method
EP0746343A1 (fr) * 1993-10-08 1996-12-11 The Regents of The University of Michigan PROCEDES ET COMPOSITIONS CONCERNANT UN REIN BIOARTIFICIEL CONVENANT POUR UNE UTILISATION $i(IN VIVO) OU $i(EX VIVO)
US5681740A (en) * 1995-06-05 1997-10-28 Cytotherapeutics, Inc. Apparatus and method for storage and transporation of bioartificial organs
US5713888A (en) * 1990-10-31 1998-02-03 Baxter International, Inc. Tissue implant systems
US5741330A (en) * 1990-10-31 1998-04-21 Baxter International, Inc. Close vascularization implant material
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