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WO1993002635A1 - Implant foramine - Google Patents

Implant foramine Download PDF

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Publication number
WO1993002635A1
WO1993002635A1 PCT/US1992/005747 US9205747W WO9302635A1 WO 1993002635 A1 WO1993002635 A1 WO 1993002635A1 US 9205747 W US9205747 W US 9205747W WO 9302635 A1 WO9302635 A1 WO 9302635A1
Authority
WO
WIPO (PCT)
Prior art keywords
chamber
cells
host
holes
implanted
Prior art date
Application number
PCT/US1992/005747
Other languages
English (en)
Inventor
Ronald W. Dudek
Ronald S. Hill
James H. Brauker
Original Assignee
Baxter International Inc.
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. filed Critical Baxter International Inc.
Priority to CA002092825A priority Critical patent/CA2092825A1/fr
Priority to JP5503566A priority patent/JPH06502577A/ja
Publication of WO1993002635A1 publication Critical patent/WO1993002635A1/fr
Priority to NO931168A priority patent/NO931168D0/no

Links

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
    • A61K9/0012—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
    • 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

Definitions

  • This invention relates to an implant device and method for vascularlzatlon of implanted, immunologically compatible biological materi al .
  • diseases are due to a lack or destruction of a specific biological system.
  • diseases include diabetes (lack of islet function), growth retardation (lack of growth hormone), other endocrine deficiencies (thyroid, parathyroid, reproductive, adrenal, pituitary), Parkinson's (lack of dopamine), hemophilia (lack of blood clotting factors), and inborn errors of metabolism (missing a specific enzyme or cofactor).
  • diabetes latitude of islet function
  • growth retardation lack of growth hormone
  • other endocrine deficiencies thyroid, parathyroid, reproductive, adrenal, pituitary
  • Parkinson's lack of dopamine
  • hemophilia lack of blood clotting factors
  • inborn errors of metabolism missing a specific enzyme or cofactor
  • correction of these disease states requires the replacement of the specific biological function.
  • the diabetic must respond to minute to minute changes in blood glucose with an appropriate release of pancreatic hormones to maintain normal blood glucose concentrations.
  • Diabetics treated with insulin do not maintain normal blood glucose levels.
  • Implantation of functionalis lets of Langerhans cures the disease, insulin therapy merely treats the disease.
  • organ-like structures in immunologically compatible patients is described by Thompson, Anderson, and Maciag in "Device for Directed Neovascularization and Method for Same," WO Patent Application No. 89/07944.
  • the key features of this approach are a biocompatible matrix, similar in structure to that of Vacanti and Langer, a coating of anglogenic growth factors which are used to induce in vivo directed neovascularization and subsequent implantation in patients.
  • the resulting structure termed an organoid, may be useful as an implantation site for cells of therapeutic importance. Alternatively, it may be possible to attach cells prior to implantation.
  • Applicants' invention is a chamber made of a biocompatible material adapted to be implanted in a host, and to substantially contain biological material immunologically compatible with the host, said chamber having a wall, said wall having holes traversing the wall where the holes have an inner diameter at the narrowest point large enough to permit a host capillary to traverse the thickness of the wall, and where said holes are numerous enough to permit said host capillary to support the viability of the biological material which may be contained therein.
  • Figure 1 Cross section drawing of a chamber used for vascularlzing tissue within the chamber.
  • the chamber is made of an outer housing, a foramenous membrane, o-ring spacer and sealing ring.
  • IP GTT Intraperltoneal glucose tolerance test
  • Results are the mean +. SEM of the curves for the 3 animals implanted with large hole chambers before implant ( ⁇ ), 1 week before explant ( ⁇ ). and 1 week after explant ( ⁇ ) .
  • IP GTT Intraperltoneal glucose tolerance test
  • Figure 9 Light micrographs of 14 day fetal syngeneic lung tissue after implantation for 21 days in a chamber with 5 micron pores. Note the well differentiated, highly vascularlzed tissue within the chamber. This pore size prevented the outgrowth of the tissue within the chamber.
  • FIG. 10 Light micrographs of 14 day fetal syngeneic lung tissue after implantation for 21 days in a chamber with 10 to 15 micron pores. Note the well differentiated, highly vascularlzed tissue within the device. This chamber also prevented the outgrowth of the implanted tissue.
  • FIG. 11 Light micrographs of recombinant tissue after implantation in epldidymal fat pads for 8 days in a chamber with large holes (90 x 170 micron holes). The recombinant shows positive immunocytochemical staining for insulin (A) and glucagon (B). In addition, there is prolific morphogenesis of tubules and a high degree of vascularlty.
  • FIG. 12 Light micrographs of pancreatic rudiments after implantation in epldidymal fat pads for 8 days in a chamber with large holes (90 x 170 micron holes). Pancreatic rudiments show insulin (A) and glucagon (B) positive cells, tubular morphogenesis and a high degree of vascularlty.
  • FIG. 13 Histological appearance of another large hole chamber (70 x 110 micron holes) after 3 days implantation. Chambers containing about 500 islets in Lewis rats produced a rapid vascular response as shown by the large vessel coursing through the center of the chamber after only 3 days in the animals. Figure 14. Histological appearance of 3 micron pore chamber after 3 days implantation. Devices containing about 500 islets in Lewis rats lacked an intimate vascularlzation response within the tissue chamber.
  • This invention is a chamber for substantially containing cells, cellular organelles or tissue.
  • the chamber is made of biocompatible material adapted for implantation in a host.
  • the chamber is constructed with holes that traverse the entire thickness of the chamber wall.
  • the holes need not be straight or uniform. They may form an Irrgeular pathway from the exterior to the interior of the chamber.
  • the holes have an inner diameter large enough to allow the ingrowth and egress of host capillaries to and from cells or tissue in the chamber.
  • This device is termed herein a foramenous chamber.
  • This chamber allows the host vascular system to support both viability and therapeutic effectiveness of biological material placed in the chamber.
  • the entire chamber need not have holes in It so long as a portion of the chamber has enough holes to support the viability of the contained material.
  • the upper limit of the hole size will vary with the particular application. If the biological material is to be completely contained in the chamber then the upper limit of the hole size will be determined by the size of the cells or material contained in the chamber. If complete containment is not necessary, then the holes may be any size which will substantially contain the biological material. If the material also contains some holes smaller than that necessary to allow capillaries through, it will not interfere with the operation of the chamber. Such smaller holes need not be avoided.
  • the contained biological material may be any cell, cell combination, organoid, organ or tissue to be implanted into a host. The biological material is preferably immunologically compatible with the host.
  • the chamber may be any host biocompatible material that can be safely implanted into the host. See for example Table I, page xi, in Concise Guide to Biomedical Polymers by J. W. Boretos (1973), listing stable and semlstable materials appropriate for use in this invention.
  • the chamber may be used for tissue or cell replacement in the correction of disease states. Allograft implants of cellular organelles or free cells to correct a disease state are currently performed most commonly by infusion into the portal circulation to allow the cells to lodge in the liver.
  • the instant invention allows use of an alternate implant site that can be easily accessed and the chamber with its contents may be removed if necessary.
  • the chamber allows the host to provide adequate nutrltinal support for the implanted tissue to correct a disease state. Accordingly, the chamber may be used for allograft transplant of human tissue.
  • This chamber may also be used to contruct a hybrid bioartlflcial organ.
  • the chamber allows the host to supply the bioartlflcial organ with an intimate vasculature so that nutrients are delivered to the organ, metabolic wastes are removed, and the therapeutic product made by the organ is delivered to the host.
  • the chamber can be used to enclose an inner intact cellular protectant membrane. Vascular elements penetrate the chamber and provide sufficient nutrient and waste exchange for the enclosed cells to survive and function to correct a diabetic animal.
  • the chamber can also be used to contain mlcroencapsulated cells or organelles to be implanted. By implanting the encapsulated tissue within the chamber a rapid vascularization will be stimulated and the capsules will be contained within a defined space for easy removal should the need arise.
  • a foramenous membrane In one embodiment of the invention the following components were used: a foramenous membrane; a housing to hold the membrane; an o-ring to provide a tissue space; and biological tissue (Figure 1).
  • the structural housing supports the membrane and provides integrity. In a prefered embodiment it is made of titanium. However, housings of Teflon, polystyrene and polypropylene have also been made and the housing can be made from alternative biocompatible materials.
  • the o-ring of appropriate thickness, such as about 10 to 250 micron, provides a space for cells or tissue. Typically the o-ring is made of silicone although o-rings of other biocompatible materials may be used.
  • Membranes with a nominal pore size of about 3 micron failed to induce a rapid vascular response wi thi n the chamber (Figure 14).
  • Vascular elements were detected in these 3 micron pore membrane devices after 3 to 9 weeks of implantation, but the vessels were occluded with inadequate blood flow to the implanted tissue. This was shown by islets implanted within a 3 micron pore membrane device falling to correct diabetic-animals ( Figures 2b, 4, 6, and 8).
  • the lower limit of nominal pore size to induce an adequate vascular response is greater than about 3 micron.
  • Membranes with nominal pore size of 5 to 15 micron induced a rapid vascular response ( Figures 9 and 10). Holes up to and including those of 90 x 170 micron induced the response ( Figures 7, 11, 12, and 13).
  • Alternative forms of the chamber are also possible. These include, but are not limited to, including a scaffolding for cellular attachment within the chamber; providing an intact immunoprotective membrane enclosing cellular elements within the chamber; using microencapsulated tissue within the device; making the o-ring of a material which will seal the membranes together eliminating the need for the housing; stacked membrane packets to provide additional space for implanted tissue; making the device in the form of hollow fibers; or sealing the membrane with techniques such as sonic welding that does not require a housing.
  • diabetic Lewis rats were implanted with large hole membrane or intact membrane devices containing isolated syngeneic islets. Implanted animals were compared to sham operated and diabetic control animals.
  • test membrane a teflon membrane with polyester fiber backing, 3.0 micron effective nominal pore size, Gore® 3 micron teflon #L10956
  • Freon-TE35 3.0 micron effective nominal pore size
  • ethanol was removed with a sterile saline wash (0.95. NaCl).
  • Membranes were transferred to culture medium (RPMI 1640 + 10% Fetal Bovine serum, FBS) and placed in a 37°C CO 2 incubator.
  • Islets from syngeneic Lewis rats were used for implantation. Following sacrifice, under aseptic conditions, the common bile duct was cannulated and the pancreas inflated with 10 ml of Hank's balanced salt solution (HBSS). The inflated pancreas was removed, cleaned and minced. Minced tissue was digested with collagenase (type V, Sigma) at 10 mg per pancreas in a 39°C water bath. Digestion was stopped with Ice-cold HBSS and the contents washed 3 times with HBSS. Islets were separated from adnar and most ductal tissue by centrifugation in a bovine serum albumin (BSA) step gradient of 29%, 26%, 23%, and 20%. Islets were washed with RPMI 1640 medium with 10% fetal bovine serum and cultured at 37°C in air/5% CO 2 for 3 to 7 days before implantation.
  • BSA bovine serum albumin
  • Islets were hand picked from the culture plates for loading the devices. Ten ul of islet suspension (approximately 2000
  • Islets were loaded into each test device. Each animal received 2 devices (4000 is lets total). Animals were anesthetized with xylazine (5 mg/kg) and ketamine (65 mg/kg) and their epldidymal fat pads isolated through a small lower abdominal incision. One device was placed on each fat pad and covered wi th the fat pad . Devi ces were hel d i n pl ace with Nexaband (CRX Medical, Inc.) tissue adhesive. The abdominal muscle was closed with suture (4-0 gut) and the skin with stainless steel wound clips.
  • the functional state of the animals was evaluated by monitoring the following parameters: change in body weight, non-fasting blood glucose, intraperltoneal glucose tolerance, and histology of the implants and pancreatic remnants at the time of sacrifice.
  • Periodic non-fasting blood glucose levels were assessed with an ExacTechTM Blood Glucose Meter (Medlsense) in blood obtained from a tall vein stick.
  • the upper limit of detection of the ExacTechTM Blood Glucose Meter is 450 mg/dl. Values reported as 450 mg/dl are a minimal estimate of the actual blood glucose concentration.
  • Intraperltoneal glucose tolerance tests IP GTT consist of an overnight fast, I. P. injection of glucose (2 g/kg body weight from a 20% glucose solution) and measuring blood glucose at 0 (before injection), 10, 30, 50, and 90 minutes. Body weights were monitored throughout the study.
  • IP GTT Intraperltoneal Glucose Tolerance Tests
  • the large hole chambers contained large numbers of well vascularlzed islets (Figure 7). Capillaries were detected within the islets themselves. The intact membrane implant was also well vascularlzed on both the inside and outside of the chamber, but large blood islands formed within the device indicating a lack of freely flowing blood. In addition, only a small number ofislets were found within the chambers ( Figure 8). Residual pancreas within the diabetic animals only contained sparse, badly damaged islet remnants.
  • the body weight changes, non-fasting blood glucose levels, IP GTT's, and histology demonstrate that the large hole implants corrected the diabetes of these 3 animals.
  • the same parameters indicate that the intact membrane implants had only limited function and did not correct the diabetic state of the 3 animals with intact implants.
  • the islets were maintained in a functional state in the large hole chambers because the chambers allow vascularlzation of the islets through the large holes in the chamber.
  • Lung tissue from day 14 of gestation was isolated, minced into approximately 1 mm 3 pieces, washed with DMEM, 20% FBS and placed in titanium chambers.
  • the membranes used for this experiment were teflon with nominal pore size of either 5 or 10 to 15 micron. Devices were placed into epldidymal fat pads, left in the animals for 21 days and then explanted. Tissue was fixed in 2.5% glutaraldehyde and processed for hlstological examination.
  • Membranes with 5 micron nominal pore size allowed the fetal lung tissue to differentiate and mature and significant vascular response to the contained tissue was evident (Figure 9). Note that with the intact 5 micron pore membrane the tissue was contained within the device and did not grow out of the pores.
  • Membranes with 10 to 15 micron nominal pores also permitted the full differentiation and maturation of the implanted tissue (Figure 10). Again, tissue was contained within the interior of the chamber and was well vascularlzed.
  • the tissue chamber devices were implanted on the epldidymal fat pad of adult male Lewis rats.
  • the epldidymal fat pad was pulled through a medial incision just anterior to the penis and laid on sterile gauze wetted with saline.
  • the chamber was placed on the fat pad and the titanium ring was glued to the fat pad with tissue adhesive.
  • Endocrine tissue also differentiated in pancreatic rudiments as evidenced by immunostaining for insulin and glucagon after 8 days implantation ( Figure 12). in all instances the implanted tissue was well vascularized. Thus, the large hol e membrane chambers were capable of supporting fetal tissue growth, morphogenesis and differentiation due to the substantial host vascularlzation.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Vascular Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Prostheses (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Une chambre fabriquée dans un matériau biocompatible, conçue pour être implantée chez un individu hôte et pouvant contenir une matière biologique compatible immunologiquement avec l'individu, comporte une paroi, des trous traversant ladite paroi, ceux-ci ayant à l'endroit le plus étroit un diamètre intérieur suffisamment grand pour permettre à un capillaire fonctionnel de l'hôte de traverser l'épaisseur de la paroi; et ces trous sont assez nombreux pour permettre audit capillaire de l'hôte de préserver la viabilité de la matière biologique contenue.
PCT/US1992/005747 1991-07-30 1992-07-09 Implant foramine WO1993002635A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CA002092825A CA2092825A1 (fr) 1991-07-30 1992-07-09 Implant muni de trous
JP5503566A JPH06502577A (ja) 1991-07-30 1992-07-09 有孔埋め込み物
NO931168A NO931168D0 (no) 1991-07-30 1993-03-29 Forameniplantat

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73763291A 1991-07-30 1991-07-30
US737,632 1991-07-30

Publications (1)

Publication Number Publication Date
WO1993002635A1 true WO1993002635A1 (fr) 1993-02-18

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Application Number Title Priority Date Filing Date
PCT/US1992/005747 WO1993002635A1 (fr) 1991-07-30 1992-07-09 Implant foramine

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EP (1) EP0555428A1 (fr)
JP (1) JPH06502577A (fr)
CA (1) CA2092825A1 (fr)
NO (1) NO931168D0 (fr)
WO (1) WO1993002635A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018906A1 (fr) * 1993-02-18 1994-09-01 New England Deaconess Hospital, Corp. Organe artificiel implantable
WO1995005452A3 (fr) * 1993-08-12 1995-03-30 Cytotherapeutics Inc Compositions et procedes ameliores pour l'administration de molecuiles a activite biologique a l'aide de cellules modifiees genetiquement comprises dans des capsules biocompatibles immuno-isolatrices
WO1996032076A1 (fr) * 1995-04-11 1996-10-17 Baxter Internatonal Inc. Dispositifs d'implantation tissulaire
US5908623A (en) * 1993-08-12 1999-06-01 Cytotherapeutics, Inc. Compositions and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules
EP2125056A4 (fr) * 2007-02-19 2014-09-24 Ticapex Ab Ensemble d'implant
US9764062B2 (en) 2008-11-14 2017-09-19 Viacyte, Inc. Encapsulation of pancreatic cells derived from human pluripotent stem cells
WO2018089011A1 (fr) 2016-11-10 2018-05-17 Viacyte, Inc Cellules d'endoderme pancréatique pdx1 dans des dispositifs d'administration de cellules et procédés associés
WO2023164171A2 (fr) 2022-02-25 2023-08-31 Viacyte, Inc. Dispositifs d'encapsulation de cellules implantables multicouches et procédés associés
WO2023177316A1 (fr) * 2022-03-18 2023-09-21 Polbionica Sp. Z O.O. Construction de renforcement et d'étanchéité pour un modèle de tissu bio-imprimé, et procédé d'assemblage de la construction de renforcement et d'étanchéité
PL132035U1 (pl) * 2024-03-12 2025-09-15 Polbionica Spółka Z Ograniczoną Odpowiedzialnością Obudowa wzmacniająca i uszczelniająca biodrukowany model tkankowy
US12427170B2 (en) 2019-09-05 2025-09-30 Crispr Therapeutics Ag Universal donor cells

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017158791A1 (fr) * 2016-03-17 2017-09-21 富士機械製造株式会社 Chambre cellulaire pour organes artificiels

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4309776A (en) * 1980-05-13 1982-01-12 Ramon Berguer Intravascular implantation device and method of using the same
WO1988003785A1 (fr) * 1986-11-20 1988-06-02 Vacanti Joseph P Neomorphogenese chimerique d'organes par implantation cellulaire controlee mettant en oeuvre des matrices artificielles
WO1991000119A1 (fr) * 1989-06-30 1991-01-10 Baxter International Inc. Dispositif implantable

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4309776A (en) * 1980-05-13 1982-01-12 Ramon Berguer Intravascular implantation device and method of using the same
WO1988003785A1 (fr) * 1986-11-20 1988-06-02 Vacanti Joseph P Neomorphogenese chimerique d'organes par implantation cellulaire controlee mettant en oeuvre des matrices artificielles
WO1991000119A1 (fr) * 1989-06-30 1991-01-10 Baxter International Inc. Dispositif implantable

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J.BIOMED.MATER.RES. vol. 17, no. 5, pages 865 - 872 G.KLOMP EA 'MACRO POROUS HYDROGEL MEMBRANES FOR A HYBRID ARTIFICIAL PANCREAS' *

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018906A1 (fr) * 1993-02-18 1994-09-01 New England Deaconess Hospital, Corp. Organe artificiel implantable
WO1995005452A3 (fr) * 1993-08-12 1995-03-30 Cytotherapeutics Inc Compositions et procedes ameliores pour l'administration de molecuiles a activite biologique a l'aide de cellules modifiees genetiquement comprises dans des capsules biocompatibles immuno-isolatrices
US5639275A (en) * 1993-08-12 1997-06-17 Cytotherapeutics, Inc. Delivery of biologically active molecules using cells contained in biocompatible immunoisolatory capsules
US5653975A (en) * 1993-08-12 1997-08-05 Cytotherapeutics, Inc. Compositions and methods for the delivery of biologically active molecules using cells contained in biocompatible capsules
US5656481A (en) * 1993-08-12 1997-08-12 Cyto Therapeutics, Inc. Compositions and methods for the delivery of biologically active molecules using cells contained in biocompatible capsules
US5676943A (en) * 1993-08-12 1997-10-14 Cytotherapeutics, Inc. Compositions and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules
US5908623A (en) * 1993-08-12 1999-06-01 Cytotherapeutics, Inc. Compositions and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules
US6264941B1 (en) 1993-08-12 2001-07-24 Neurotech S.A. Compositions for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules
WO1996032076A1 (fr) * 1995-04-11 1996-10-17 Baxter Internatonal Inc. Dispositifs d'implantation tissulaire
EP2125056A4 (fr) * 2007-02-19 2014-09-24 Ticapex Ab Ensemble d'implant
US9764062B2 (en) 2008-11-14 2017-09-19 Viacyte, Inc. Encapsulation of pancreatic cells derived from human pluripotent stem cells
US9913930B2 (en) 2008-11-14 2018-03-13 Viacyte, Inc. Encapsulation of pancreatic cells derived from human pluripotent stem cells
US10272179B2 (en) 2008-11-14 2019-04-30 Viacyte, Inc. Encapsulation of pancreatic cells derived from human pluripotent stem cells
US11660377B2 (en) 2008-11-14 2023-05-30 Viacyte, Inc. Cryopreserved in vitro cell culture of human pancreatic progenitor cells
WO2018089011A1 (fr) 2016-11-10 2018-05-17 Viacyte, Inc Cellules d'endoderme pancréatique pdx1 dans des dispositifs d'administration de cellules et procédés associés
EP4595951A2 (fr) 2016-11-10 2025-08-06 ViaCyte, Inc. Cellules d'endoderme pancréatique pdx1 dans des dispositifs d'administration de cellules et procédés associés
US12427170B2 (en) 2019-09-05 2025-09-30 Crispr Therapeutics Ag Universal donor cells
WO2023164171A2 (fr) 2022-02-25 2023-08-31 Viacyte, Inc. Dispositifs d'encapsulation de cellules implantables multicouches et procédés associés
WO2023177316A1 (fr) * 2022-03-18 2023-09-21 Polbionica Sp. Z O.O. Construction de renforcement et d'étanchéité pour un modèle de tissu bio-imprimé, et procédé d'assemblage de la construction de renforcement et d'étanchéité
PL132035U1 (pl) * 2024-03-12 2025-09-15 Polbionica Spółka Z Ograniczoną Odpowiedzialnością Obudowa wzmacniająca i uszczelniająca biodrukowany model tkankowy

Also Published As

Publication number Publication date
EP0555428A1 (fr) 1993-08-18
CA2092825A1 (fr) 1993-01-31
NO931168L (no) 1993-03-29
NO931168D0 (no) 1993-03-29
JPH06502577A (ja) 1994-03-24

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