DK2842581T3 - Sæklignende struktur med parakrinaktivitet og fremgangsmåde til fremstilling deraf - Google Patents
Sæklignende struktur med parakrinaktivitet og fremgangsmåde til fremstilling deraf Download PDFInfo
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- DK2842581T3 DK2842581T3 DK13182437.7T DK13182437T DK2842581T3 DK 2842581 T3 DK2842581 T3 DK 2842581T3 DK 13182437 T DK13182437 T DK 13182437T DK 2842581 T3 DK2842581 T3 DK 2842581T3
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- cells
- paracrine factor
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- heart
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Claims (15)
1. Sæklignende struktur der er egnet til at omslutte mindst en del af hjertet hos et pattedyr, hvilken sæklignende struktur omfatter et in vitro manipuleret væv kendetegnet ved, at mindst en del af det manipuleret væv omfatter skabelonmateriale og genmodificerede celler, hvorved de genmodificerede celler indeholder et gen der koder for en pa rakri nfaktor, idet genet der koder for parakrinfaktoren er styret af et kemisk inducerbart promotorsystem valgt fra et tetracyclin-baseret system, et rapamycin-baseret system, et progesteron-baseret system, og et ecdyson-baseret system, eller et heterologt promotorsystem som ikke er naturligt forekommende i cellen, hvor de genmodificerede celler er celler valgt fra fibroblaster, glatte muskelceller, endotelceller, mesenkymale stamceller, hjertestamceller, pericytter og leukocytter, og hvor parakrinfaktoren er en parakrinfaktor valgt fra IGF-1, VEGF, HGF, PDGF, SDF-1 eller miRNA, med kardio-beskyttende og/eller kardio-regenererings inducerende aktivitet.
2. Sæklignende struktur ifølge krav 1 hvor de genmodificerede celler er allogene celler eller autologe celler.
3. Sæklignende struktur ifølge et hvilket som helst af de foregående krav hvor det manipulerede væv endvidere omfatter myocytter, og/eller andre celler fra hjertevævet forskellige fra hjertemyocytter.
4. Sæklignende struktur ifølge krav 3 hvor de yderligere myocytter er hjertemyocytter.
5. Sæklignende struktur ifølge et hvilket som helst af de foregående krav hvor parakrinfaktoren er valgt fra miR133, miRl, miR499, miR-208, miR-199a-3p, miR-590-3p, miR1825, miR33b.
6. Sæklignende struktur ifølge et hvilket som helst af de foregående krav hvor strukturen har kontraktionsegenskaber.
7. Sæklignende struktur ifølge et hvilket som helst af kravene 1 til 5 hvor genet der koder for en parakrinfaktor er styret af den heterologe promotor der ikke er naturligt forekommende i cellen.
8. Sæklignende struktur der er egnet til at omslutte mindst en del af hjertet hos et pattedyr, hvillken sæklignendestruktur omfatter et manipuleret væv kendetegnet ved, at mindst en del af det manipuleret væv omfatter genmodificerede celler, hvorved de genmodificerede celler indeholder et gen der koder for en parakrinfaktor, idet genet der koder for parakrinfaktoren er styret af et inducerbart promotorsystem eller et heterologt promotorsystem der ikke er naturligt forekommende i cellen, hvor de genmodificerede celler er celler valgt fra fibroblaster, glatte muskelceller, endotelceller, mesenkymale stamceller, hjertestamceller, pericytter, og leukocytter, og hvor parakrinfaktoren er en parakrinfaktor valgt fra IGF-1, VEGF, HGF, PDGF, SDF-1 eller miRNA, med kardio-beskyttende og/eller kardio-regenererings inducerende aktivitet, især, ifølge et hvilket som helst af de foregående krav, til anvendelse i terapeutiske anvendelser.
9. Anvendelse af en sæklignende struktur der er egnet til at omslutte mindst en del af hjertet hos et pattedyr til anvendelse i sygdomsmodellering og lægemiddeludviklingsanvendelser, hvilken sæklignendestruktur omfatter et manipuleret væv kendetegnet ved, at mindst en del af det manipulerede væv omfatter genmodificerede celler, hvorved de genmodificerede celler indeholder et gen der koder for en parakrinfaktor, idet genet der koder for parakrinfaktoren er styret af et inducerbart promotorsystem eller et heterologt promotorsystem der ikke er naturligt forekommende i cellen, hvor de genmodificerede celler er celler valgt fra fibroblaster, glatte muskelceller, endotelceller, mesenkymale stamceller, hjertestamceller, pericytter, og leukocytter, og hvor parakrinfaktoren er en parakrinfaktor valgt fra IGF-1, VEGF, HGF, PDGF, SDF-1 eller miRNA med kardio-beskyttende og/eller kardio-regenererings inducerende aktivitet, især, ifølge et hvilket som helst af kravene 1 til 7.
10. Fremgangsmåde til fremstilling af en sæklignende struktur der er egnet til at omslutte mindst en del af hjertet hos et pattedyr og omfattende manipuleret væv, idet det manipulerede væv omfatter et skabelon-materiale og genmodificerede celler, der indeholder et gen der koder for en parakrinfaktor og idet genet er styret af et kemisk inducerbart promotorsystem valgt fra et tetracyclin-baseret system, et rapamycin-baseret system, et progesteron-baseret system, og et ecdyson-baseret system, eller et heterologt promotorsystem der ikke er naturligt forekommende i cellen, hvilken fremgangsmåde omfatter trinnene a) at tilvejebringe en matrix med en fordybning i en overflade af matricen, hvilken fordybning har passende dimensioner til at rumme et defineret rekonstitutionsvolumen for dannelsen af den sæklignende struktur, b) at tilvejebringe et element med dimensioner svarerende til de ønskede dimensioner af indersiden af den sæklignende struktur der skal dannes, og at placere elementet i fordybningen af matricen således at elementet er anbragt med afstand til væggene i fordybningen for at danne en afstand mellem elementet og væggene i fordybningen svarende til rekonstitutionsvolumenet der er nødvendig for dannelse af en sæklignende struktur, c) at deponere en rekonstitutionsblanding i fordybningen, hvilken rekonstitutionsblanding omfatter pattedyrsceller, såsom allogene celler, eller autologe celler, og egnet skabelon-materiale der kan inkuberes for at danne en manipuleret vævsstruktur omfattende cellerne, d) at inkubere rekonstitutionsblandingen indtil vævskonstruktionen dannes inden i matrixfordybningen mellem elementet og matricen, e) at udskifte dyrkningsmediet når den sæklignende konstruktion er blevet dannet rundt om hovedelementet, f) at fjerne elementet med vævskonstruktionen klæbende dertil fra matrixfordybningen, og g) at separere vævskonstruktionen fra elementet, hvor mindst en del af pattedyrscellerne der forekommer i den manipulerede vævsstruktur er genmodificerede celler, hvorved de genmodificerede celler indeholder et gen der koder for en parakrinfaktor og idet genet er styret af et kemisk inducerbart promotorsystem valgt fra et tetracyclin-baseret system, et rapamycin-baseret system, et progesteron-baseret system, og et ecdyson-baseret system, eller et heterologt promotorsystem der ikke er naturligt forekommende i cellen, hvor de genmodificerede celler er celler valgt fra fibroblaster, glatte muskelceller, endotelceller, mesenkymale stamceller, hjertestamceller, pericytter og leukocytter eller precursorceller til disse celler, og hvor parakrinfaktoren er en parakrinfaktor valgt fra IGF-1, VEGF, HGF, PDGF, SDF-1 eller miRNA, med kardio-beskyttende og/eller kardio-regenererings inducerende aktivitet.
11. Fremgangsmåde til fremstilling af den sæklignende struktur ifølge krav 10 hvor elementet er en oppustelig struktur.
12. Fremgangsmåde ifølge krav 10 eller 11 hvor strukturen efter trin h) udsættes for trækbelastning.
13. Fremgangsmåde ifølge krav 12 hvor trækbelastningen er statisk, fasisk eller auxotonisk belastning eller en kombination deraf.
14. Anvendelse af genmodificerede celler, til fremstilling afen sæklignende struktur der er egnet til at omslutte mindst en del af hjertet hos et pattedyr hvor cellerne er genmodificerede celler indeholdende et gen der koder for en parakrinfaktor og/eller et gen der koder for RNA, såsom miRNA, og hvilket gen er styret af et kemisk inducerbart promotorsystem valgt fra et tetracyclin-baseret system, et rapamycin-baseret system, et progesteron-baseret system, og et ecdyson-baseret system, hvor de genmodificerede celler er celler valgt fra fibroblaster, glatte muskelceller, endotelceller, mesenkymale stamceller, hjertestamceller, pericytter og leukocytter eller precursorceller til disse celler, og hvor parakrinfaktoren er en parakrinfaktor valgt fra IGF-1, VEGF, HGF, PDGF, SDF-1 eller miRNA, med kardio-beskyttende og/eller kardio-regenererings inducerende aktivitet.
15. Anvendelse af genmodificerede celler, ifølge krav 14 hvor cellerne er allogene eller autologe celler fra patienten der forventes at modtage den sæklignende struktur.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13182437.7A EP2842581B1 (en) | 2013-08-30 | 2013-08-30 | Pouch-like structure with paracrine activity and method for its preparation |
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| DK2842581T3 true DK2842581T3 (da) | 2019-02-18 |
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| EP (1) | EP2842581B1 (da) |
| DK (1) | DK2842581T3 (da) |
| ES (1) | ES2706401T3 (da) |
| SG (1) | SG10201405325RA (da) |
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| US8579964B2 (en) | 2010-05-05 | 2013-11-12 | Neovasc Inc. | Transcatheter mitral valve prosthesis |
| US9554897B2 (en) | 2011-04-28 | 2017-01-31 | Neovasc Tiara Inc. | Methods and apparatus for engaging a valve prosthesis with tissue |
| US9308087B2 (en) | 2011-04-28 | 2016-04-12 | Neovasc Tiara Inc. | Sequentially deployed transcatheter mitral valve prosthesis |
| US9345573B2 (en) | 2012-05-30 | 2016-05-24 | Neovasc Tiara Inc. | Methods and apparatus for loading a prosthesis onto a delivery system |
| US9572665B2 (en) | 2013-04-04 | 2017-02-21 | Neovasc Tiara Inc. | Methods and apparatus for delivering a prosthetic valve to a beating heart |
| DK2840132T3 (da) | 2013-08-22 | 2017-02-20 | Georg-August-Universität Göttingen Stiftung Öffenlichen Rechts Universitätsmedizin | Fremgangsmåde til fremstilling af konstrueret hjertemuskel (EHM) |
| WO2017100927A1 (en) | 2015-12-15 | 2017-06-22 | Neovasc Tiara Inc. | Transseptal delivery system |
| EP3184128B1 (en) * | 2015-12-21 | 2019-12-11 | Heinrich-Heine-Universität Düsseldorf | Method for producing a support device |
| CN108882981B (zh) | 2016-01-29 | 2021-08-10 | 内奥瓦斯克迪亚拉公司 | 用于防止流出阻塞的假体瓣膜 |
| EP3527212A4 (en) * | 2016-10-13 | 2020-05-06 | National Center of Neurology and Psychiatry | Myogenesis inducing agent |
| CN109996581B (zh) | 2016-11-21 | 2021-10-15 | 内奥瓦斯克迪亚拉公司 | 用于快速收回经导管心脏瓣膜递送系统的方法和系统 |
| US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
| CA3073834A1 (en) | 2017-08-25 | 2019-02-28 | Neovasc Tiara Inc. | Sequentially deployed transcatheter mitral valve prosthesis |
| AU2019374743B2 (en) | 2018-11-08 | 2022-03-03 | Neovasc Tiara Inc. | Ventricular deployment of a transcatheter mitral valve prosthesis |
| CA3132873C (en) | 2019-03-08 | 2024-07-02 | Neovasc Tiara Inc | RECOVERABLE PROSTHESIS PLACEMENT SYSTEM |
| WO2020206012A1 (en) | 2019-04-01 | 2020-10-08 | Neovasc Tiara Inc. | Controllably deployable prosthetic valve |
| CN113924065A (zh) | 2019-04-10 | 2022-01-11 | 内奥瓦斯克迪亚拉公司 | 具有自然血流的假体瓣膜 |
| US11779742B2 (en) | 2019-05-20 | 2023-10-10 | Neovasc Tiara Inc. | Introducer with hemostasis mechanism |
| EP3986332A4 (en) | 2019-06-20 | 2023-07-19 | Neovasc Tiara Inc. | FLAT ARTIFICIAL MITRAL VALVE |
| DK3988138T3 (da) * | 2020-10-22 | 2024-02-26 | Georg August Univ Goettingen Stiftung Oeffentlichen Rechts Univsmedizin | Flerlaget kunstig hjertemuskel |
| EP4386384A1 (en) | 2022-12-15 | 2024-06-19 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | Potency assay for pharmaceutical products |
Family Cites Families (3)
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|---|---|---|---|---|
| DE10003521A1 (de) | 2000-01-27 | 2001-08-09 | Medigene Ag | Vorrichtung zum Herstellen eines dreidimensionalen Matrixkörpers, Multi-Well-Platte, Lösung zum Kultivieren von Säugerkardiomyocyten, Verfahren zum Kultivieren einer Zellkultur, Vorrichtung für die Messung isometrischer Kraftparameter von Zellkulturen sowie Verfahren zum meßbaren Verfolgen von Kontraktionen eines in eine Trägersubstanz eingelagerten Zellgewebes |
| US9018440B2 (en) * | 2006-10-27 | 2015-04-28 | Stowers Institute For Medical Research | Fluorescent mouse model |
| EP1920789A1 (en) | 2006-11-11 | 2008-05-14 | Universitätsklinikum Hamburg-Eppendorf | Pouch-like construct comprising mammalian tissue |
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