DE4001319A1 - Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod. - Google Patents

Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod.

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Publication number
DE4001319A1
DE4001319A1 DE19904001319 DE4001319A DE4001319A1 DE 4001319 A1 DE4001319 A1 DE 4001319A1 DE 19904001319 DE19904001319 DE 19904001319 DE 4001319 A DE4001319 A DE 4001319A DE 4001319 A1 DE4001319 A1 DE 4001319A1
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Germany
Prior art keywords
reactor
active substances
cells
biologically active
sensor
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Application number
DE19904001319
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German (de)
Inventor
Jakob Dr Bodziony
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Individual
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Priority to DE19904001319 priority Critical patent/DE4001319A1/en
Priority to DE19904002559 priority patent/DE4002559A1/en
Priority to DE19904011100 priority patent/DE4011100A1/en
Publication of DE4001319A1 publication Critical patent/DE4001319A1/en
Ceased legal-status Critical Current

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Classifications

    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Prostheses (AREA)

Abstract

An implantable bio-artificial organ capable of secreting biologically active substances, esp. hormones, has a sensor position (A) implanted in a vein or artery and consisting of a hollow fibre coated with endo- or mesothelial cells, and connected e.g. by silicon capillaries with a reactor portion (13) implanted in the tissues ot a bodily cavity. The reactor portion has one or more hollow fibres contg. cells which release active substances. Biological signals and metabolic substances can flow between the two fibre elements. Implants function as endocrine glands. USE/ADVANTAGE - Suitable esp. for transplanting pancreatic islands in diabetes treatment. More reliable than known semi-permeable diffusion chambers.

Description

Gattung des AnmeldungsgegenstandesGenre of the object of registration

Die Erfindung betrifft ein implantierbares und aus semipermeablem Material gestaltetes bio-artifizielles Organ, das zur Sekretion von biologisch aktiven Substanzen fähig ist. Dieses bio-artifizielle Organ besteht aus einem in die Arterie oder in die Vene implantierten Sensorteil (eine Hohlfaser mit der Beschichtung von Endo- und Mesothelialzellen) und aus einem in das Gewebe oder in den Körperraum implantierten Reaktorteil (meistens eine oder mehrere Hohlfasern, mit Zellen, die biologisch aktive Substanzen sezernieren können), welche so miteinander verbunden sind, daß der Durchfluß von biologischen Signalen und von metabolischen Substanzen möglich ist.The invention relates to an implantable and semi-permeable material designed bio-artificial organ for the secretion of biologically active Substances is capable. This bio-artificial organ consists of one in the Artery or sensor part implanted in the vein (a hollow fiber with the Coating of endo- and mesothelial cells) and from one into the tissue or part of the reactor implanted in the body (usually one or more Hollow fibers, with cells that can secrete biologically active substances), which are so interconnected that the flow of biological Signals and of metabolic substances is possible.

Angaben zur GattungInformation on the genus

Das vorgegebene implantable bio-artifizielle Organ soll vor allem die Funktion der beschädigten endokrinen Organe (z. B. Langerhansche Inseln des endokrinen Teils des Pankreas, Nebenschilddrüse, Hypophyse usw.) ersetzen. Es kann auch in allen Situationen, wo die Sekretion der biologisch aktiven Substanzen nötig ist, angewandt werden.The given implantable bio-artificial organ is primarily intended to function the damaged endocrine organs (e.g. Langerhan Islands of the endocrine Replace part of the pancreas, parathyroid, pituitary, etc.). It can also in all situations where the secretion of the biologically active substances is necessary to be applied.

Stand der TechnikState of the art

Bisherige Versuche der Bildung der bio-artifiziellen implantablen Organe, welche biologisch aktive Substanzen sezernieren, waren vor allem zur Konstruk­ tion von semipermeablen Diffusionskammern begrenzt. Diese Kammern enthielten Zellen, die biologisch aktive Substanzen produzierten (Jolley und Mitarb., 1977; Gates und Lazarus, 1977; Theodoru und Howell 1979; Bodziony und Mitarb., 1985; Bodziony und Stanosek, 1985; Kojima und Mitarb., 1987). Previous attempts at the formation of bio-artificial implantable organs, which biologically active substances secrete were mainly for construct tion limited by semipermeable diffusion chambers. These chambers contained Cells that produced biologically active substances (Jolley et al., 1977; Gates and Lazarus, 1977; Theodoru and Howell 1979; Bodziony and co-workers, 1985; Bodziony and Stanosek, 1985; Kojima et al., 1987).  

Kritik des Standes der TechnikCritique of the state of the art

Bio-artifizielle Organe, mit Zellen, die biologisch aktive Substanzen sezer­ nieren und mit der Umgebung nur auf dem Weg der Diffusion kommunizieren, was im Fall der semipermeablen Kammern stattfindet, können leider nicht die auf sie gesetzten Erwartungen erfüllen. Unzureichender Zufluß der Nähr­ stoffe (Garvey und Mitarb., 1979), die Fremdkörperreaktion (Theodoru und Mitarb., 1980; Bodziony und Stanosek, 1985) und die verlangsamte Übertragung des biologischen Signals (Theodoru und Howell, 1979) sind Hauptursachen für die Einstellung der Hormonsekretion und das Absterben der Zellen.Bio-artificial organs, with cells that secrete biologically active substances kidneys and communicate with the environment only by diffusion, Unfortunately, what happens in the case of semi-permeable chambers cannot meet the expectations placed on them. Inadequate nutrient inflow substances (Garvey and co-workers, 1979), the foreign body reaction (Theodoru and Coworker, 1980; Bodziony and Stanosek, 1985) and the slowed down transmission of the biological signal (Theodoru and Howell, 1979) are the main causes of the cessation of hormone secretion and cell death.

Aufgabetask

Die Konstruktion eines implantierbaren bio-artifiziellen Organs, das zur Sekretion von biologisch aktiven Substanzen fähig ist. Dieses Organ soll aus einem in die Arterie oder in die Vene implantierten Sensorteil, das schnellen Austausch von biologischen Signalen und von metabolischen Substanzen durch die Ultrafiltration ermöglicht und aus einem in das Gewebe oder in den Körperraum implantierten Reaktorteil mit Zellen, die biologisch aktive Substanzen produzieren, bestehen. Beide Teile sollen so verbunden werden, daß die Übertragung von biologischen Signalen und von Nährstoffen weniger als 15 min dauert.The construction of an implantable bio-artificial organ Secretion of biologically active substances is capable. This organ is supposed to from a sensor part implanted in the artery or vein, the rapid exchange of biological signals and metabolic substances made possible by the ultrafiltration and from one into the tissue or in the body part implanted reactor part with cells that are biologically active Produce substances, exist. Both parts should be connected that the transmission of biological signals and of nutrients less lasts for more than 15 minutes.

Lösungsolution

Diese Aufgabe wird erfindungsgemäß dadurch gelöst, daß das entsprechend der vorherigen Patentanmeldung (Bodziony, 1989) anfertigte Sensorteil mit dem Reaktorteil, wie auf dem Bild 1 und 2 gezeigt, durch die Silikonkapillaren verbunden ist. Der Durchfluß des Perfusionsmedium ist durch die entsprechende Pumpe in dieser Weise erzwungen, daß es zuerst im Sensorteil auf dem Weg der Ultrafiltration und Diffusion zum Austausch von Nährstoffen und von biologi­ schen Signalen (z. B. Glukose, Ca++) kommt und danach das mit dem Plasma bio­ chemisch ausgeglichene Medium zum Reaktorteil überpumpt wird. Im Reaktorteil (meistens eine oder mehrere Hohlfasern) sind die allo- oder xenogenen Zellen, die biologisch aktive Substanzen produzieren, in dieser Weise von außen oder von innen angebracht, daß ihre mehrjährige Funktion möglich ist. Die entspre­ chenden biologisch aktiven Substanzen beeinflussen meistens das Niveau des biologischen Signals (z. B. senkt das Insulin die Konzentration von Glukose, Parathormon erhöht die Konzentration von CA++, usw.) und schließen nach der Ultrafiltration und Diffusion aus dem Reaktorteil die Rückkopplungschleife. This object is inventively achieved in that according to the previous patent application (Bodziony, 1989) anfertigte sensor part with the part of the reactor, as shown on the figure 1 and 2, is connected by the Silikonkapillaren. The flow of the perfusion medium is forced by the corresponding pump in such a way that it first comes to the exchange of nutrients and biological signals (e.g. glucose, Ca ++ ) in the sensor part on the way of ultrafiltration and diffusion and then that with the plasma bio-chemically balanced medium is pumped over to the reactor part. In the reactor part (usually one or more hollow fibers), the allo- or xenogenic cells that produce biologically active substances are attached from the outside or from the inside in such a way that their multi-year function is possible. The corresponding biologically active substances mostly influence the level of the biological signal (e.g. insulin lowers the concentration of glucose, parathyroid hormone increases the concentration of CA ++ , etc.) and closes the feedback loop after ultrafiltration and diffusion from the reactor part .

Erzielbare VorteileAchievable advantages

Das implantierbare bio-artifizielle Organ ermöglicht die mit dem positiven und negativen Feedback regulierte Sekretion der biologisch aktiven Substanzen. Das angewandte semipermeable Material ist als sog. biomechanische Barriere benutzt (Bodziony und Mitarb., 1985), was die Verwendung von allo- und xeno­ genen Zellen möglich macht. Der Gegenstand der Erfindung ist durch die Her­ stellung des bio-artifiziellen Organs mit allo- oder xenogenen Zellen, die biologisch aktive Substanzen produzieren, gewerblich anwendbar. Dieses bioartifizielle Organ kann die Funktion der beschädigten endokrinen Organe (z. B. Langerhanssche Inseln, Nebenschilddrüse, Hypophyse) ersetzen.The implantable bio-artificial organ enables those with the positive and negative feedback regulated secretion of the biologically active substances. The semi-permeable material used is a so-called biomechanical barrier used (Bodziony and Mitarb., 1985), what the use of allo- and xeno gene cells possible. The object of the invention is through the Her Position of the bio-artificial organ with allo- or xenogenic cells that Produce biologically active substances, industrially applicable. This bioartificial organ can damage the function of damaged endocrine organs (e.g. Langerhans Islands, parathyroid gland, pituitary).

Beschreibung des AusführungsbeispielsDescription of the embodiment

Abb. 1 und 2 zeigen in einer experimentellen (Abb. 1) und in einer klinischen Situation das oben beschriebene bio-artifizielle Organ. Fig. 1 and 2 show the above-described bio-artificial organ in an experimental ( Fig. 1) and in a clinical situation.

Ein in die Vene im­ plantiertes Sensorteil (A Hohlfaser mit der Beschichtung von Zellen, die mehrjährige Implantation in Arterien und Venen ermöglichen) ist durch Silikon­ kapillaren (C) mit einem in das Nierengewebe implantierten Reaktorteil (B) verbunden. Dieses Reaktorteil enthält allogene Langerhanssche Inseln, die Insulin, Glukagon und Somatostatin, wichtigste Hormone des Kohlenhydratstoff­ wechsel sezernieren. Das Perfusionsmedium wird durch die Pumpe (D) in Bewegung gesetzt und zuerst wird das Sensorteil perfundiert, wo die biochemische Aus­ gleichung mit dem Plasma stattfindet. Danach werden die isolierten Langerhan­ sschen Inseln im Reaktorteil (B) perfundiert. Diese Inseln antworten auf die Erhöhung der Konzentration der Glukose im Perfusionsmedium mit der entspre­ chenden Insulinfreisetzung, die so lange dauert, bis die Glukosekonzentration wieder gesunken ist. Die Antwort auf eine intravenöse Glukosebelastung dauert weniger als 10 min, was die präzise Regulierung der Glukose- und Insulinkon­ zentration ermöglicht. One in the vein in the planted sensor part (A hollow fiber with the coating of cells that allow perennial implantation in arteries and veins) is through silicone capillaries (C) with a reactor part (B) implanted in the kidney tissue connected. This part of the reactor contains allogeneic Langerhans islands Insulin, glucagon and somatostatin, the main hormones of the carbohydrate secrete change. The perfusion medium is moved by the pump (D) set and first the sensor part is perfused where the biochemical out equation with the plasma takes place. After that, the isolated Langerhan islands in the reactor part (B) perfused. These islands respond to the Increase the concentration of glucose in the perfusion medium with the corresponding appropriate insulin release that lasts until the glucose concentration has dropped again. The answer to intravenous glucose exposure is long less than 10 min, which is the precise regulation of glucose and insulin con allows concentration.  

FundstellenSites

1. Bodziony J., Gasior U., Stanosek J.: Funktionsbeurteilung isolierter Langerhansscher Insel in semipermeablen Kammern. Z. exp. Chir. Transplant. künstl. Organe, 1985, 18/4, 204-214.1. Bodziony J., Gasior U., Stanosek J .: Functional evaluation of isolated Langerhans Island in semi-permeable chambers. Z. exp. Chir. Transplant. artificial Organs, 1985, 18/4, 204-214.

2. Bodziony J., Stanosek J.: Die Behandlung des Diabetes durch Implantationen von isolierten Langerhansschen Insel in semipermeablen Kammern. Z. exp. Chir. Transplant. künstl. Organe, 1985, 18/4, 215-223.2. Bodziony J., Stanosek J .: Treatment of diabetes by implantation from isolated Langerhans Island in semipermeable chambers. Z. exp. Chir. Transplant. artificial Organs, 1985, 18/4, 215-223.

3. Bodziony J.: Hohlfaser mit der Beschichtung von Zellen, die mehrjährige Implantation in Arterien und Venen ermöglichen. Deutsches Patentamt, Patent­ anmeldung P 39 41 873.1.3. Bodziony J .: hollow fiber with the coating of cells, the perennial Allow implantation in arteries and veins. German Patent Office, patent registration P 39 41 873.1.

4. Gates R.J., Lazarus N.R.: Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pan­ creatic tissue. Lancet, 1977, 17, 1257-1259.4. Gates R.J., Lazarus N.R .: Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pan creative tissue. Lancet, 1977, 17, 1257-1259.

5. Garvey J.F.W., Morris P.J., Finch D.R.A., Millard P.R., Poole M.: Experi­ mental pancreas transplantation. Lancet, 1979, 971-972.5. Garvey J.F.W., Morris P.J., Finch D.R.A., Millard P.R., Poole M .: Experi mental pancreas transplantation. Lancet, 1979, 971-972.

6. Jolley W.B., Hinshaw D.B., Call T.W., Alrord L.S.: Xenogeneic pancreatic islet transplantation in proteolytic enzyme-bounded diffusion chambers in diabetic rats. Transplantation Proceedings, 1979, 9/1, 363-365.6. Jolley W.B., Hinshaw D.B., Call T.W., Alrord L.S .: Xenogeneic pancreatic islet transplantation in proteolytic enzyme-bounded diffusion chambers in diabetic rats. Transplantation Proceedings, 1979, 9/1, 363-365.

7. Kojima Y., Fukushima W., Note M., Kinoshita H., Nahagawara G.: Xenogeneic pancreatic islet transplantation using a millipore diffusion chamber. Trans­ plantation Proceedings, 1987, 19/1, 981-983.7. Kojima Y., Fukushima W., Note M., Kinoshita H., Nahagawara G .: Xenogeneic pancreatic islet transplantation using a millipore diffusion chamber. Trans plantation proceedings, 1987, 19/1, 981-983.

8. Theodoru N.A., Howell S.L.: An assesment of diffusion chambers for use in pancreatic islet cell transplantation. Transplantation, 1979, 27/5, 350- 352.8. Theodoru N.A., Howell S.L .: An assesment of diffusion chambers for use in pancreatic islet cell transplantation. Transplantation, 1979, 27/5, 350- 352.

9. Theodoru N.A., Vrbova H., Tyhurst M., Howell S.L.: Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplan­ tations in rats. Diabetologia, 1980, 18, 313-317.9. Theodoru N.A., Vrbova H., Tyhurst M., Howell S.L .: Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplan tations in rats. Diabetologia, 1980, 18, 313-317.

Claims (1)

Ein implantierbares und aus semipermeablem Material gestaltetes bio-artifi­ zielles Organ, fähig zur Sekretion von biologisch aktiven Substanzen (vor allem Hormone), gekennzeichnet durch ein in die Arterie oder in die Vene implantiertes Sensorteil (eine Hohlfaser mit der Beschichtung von Endo- oder Mesothelial Zellen) und durch ein in das Gewebe oder in den Körperraum im­ plantiertes Reaktorteil (meistens eine oder mehrere Hohlfasern, mit Zellen, die biologisch aktive Substanzen sezernieren können), so miteinander verbun­ den, daß der Durchfluß von biologischen Signalen und von metabolischen Sub­ stanzen möglich ist.An implantable bio-artifical organ made of semi-permeable material, capable of secretion of biologically active substances (especially hormones), characterized by a sensor part implanted in the artery or in the vein (a hollow fiber with the coating of endo- or mesothelial cells ) and by a in the tissue or in the body in the planted reactor part (usually one or more hollow fibers, with cells that can secrete biologically active substances), so interconnected that the flow of biological signals and metabolic substances is possible .
DE19904001319 1990-01-18 1990-01-18 Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod. Ceased DE4001319A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DE19904001319 DE4001319A1 (en) 1990-01-18 1990-01-18 Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod.
DE19904002559 DE4002559A1 (en) 1990-01-18 1990-01-30 Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substances
DE19904011100 DE4011100A1 (en) 1990-01-18 1990-04-06 Extracorporeal or implantable artificial organs - esp. to replace kidney or liver function, with semipermeable membrane controlled by biological and metabolic substances

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19904001319 DE4001319A1 (en) 1990-01-18 1990-01-18 Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod.

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DE4001319A1 true DE4001319A1 (en) 1991-07-25

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4123629A1 (en) * 1990-08-06 1992-02-20 Jakob Dr Bodziony Implantable semi-permeable bio-artificial organ - allowing biological signal and metabolic substance flow by pressure gradient
WO1995000654A1 (en) * 1993-06-18 1995-01-05 Beth Israel Hospital Association Mesothelial cell gene therapy
US11529463B2 (en) 2017-05-02 2022-12-20 Seraip Ag In-body perfusion system

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3422639C2 (en) * 1984-06-19 1986-07-10 Gebrüder Sulzer AG, Winterthur Glandular prosthesis
GB2185408A (en) * 1986-01-16 1987-07-22 Rhode Island Hospital Neovascularization
EP0259536A2 (en) * 1986-09-11 1988-03-16 BAXTER INTERNATIONAL INC. (a Delaware corporation) Biological implant with textured surface
EP0286284A1 (en) * 1987-03-30 1988-10-12 Brown University Research Foundation Semipermeable nerve guidance channels
WO1989007425A2 (en) * 1988-02-17 1989-08-24 Genethics Limited Clinical developments using amniotic cells

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3422639C2 (en) * 1984-06-19 1986-07-10 Gebrüder Sulzer AG, Winterthur Glandular prosthesis
GB2185408A (en) * 1986-01-16 1987-07-22 Rhode Island Hospital Neovascularization
DE3701148C2 (en) * 1986-01-16 1989-08-31 Rhode Island Hospital, Providence, R.I., Us
EP0259536A2 (en) * 1986-09-11 1988-03-16 BAXTER INTERNATIONAL INC. (a Delaware corporation) Biological implant with textured surface
EP0286284A1 (en) * 1987-03-30 1988-10-12 Brown University Research Foundation Semipermeable nerve guidance channels
WO1989007425A2 (en) * 1988-02-17 1989-08-24 Genethics Limited Clinical developments using amniotic cells
EP0333328A2 (en) * 1988-02-17 1989-09-20 Genethics Limited Clinical developments using amniotic cells

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4123629A1 (en) * 1990-08-06 1992-02-20 Jakob Dr Bodziony Implantable semi-permeable bio-artificial organ - allowing biological signal and metabolic substance flow by pressure gradient
WO1995000654A1 (en) * 1993-06-18 1995-01-05 Beth Israel Hospital Association Mesothelial cell gene therapy
US5645829A (en) * 1993-06-18 1997-07-08 Beth Israel Hospital Association Mesothelial cell gene therapy
US6068837A (en) * 1993-06-18 2000-05-30 Beth Israel Hospital Association Mesothelial cell gene therapy
US11529463B2 (en) 2017-05-02 2022-12-20 Seraip Ag In-body perfusion system

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