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REVERSIBLY IMMORTALISED OLFACTORY ENSHEATHING GLIA AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAMECM Patents

Índice de la ficha

Updated at
24/07/2026
Numero publicacion
EP.1654352.A1
Fecha publicacion
10/05/2006
Numero solicitud
EP20040743484

En detalle

Resumen

The invention relates to the basis the capability of the olfactory sense initial sound cell (OEG) accelerating the axis-cylinder regeneration from the mature mammal central nervous system (CNS). The specific capability is caused by the combination combining the ability accompanying the axis-cylinder growing in CNS reducing the estimation phase neuroglia cell scar and is damaged of multiple factors for example the molecular composition of the cell membrane and/or the capability secreting a part molecule. The cell strain which became from the first human OEG with immortalization was developed these inventors. By cell was cultivated from the post human tissue of donor and it reversibled using in system it immortalized. It selected with the capability accelerating the axis-cylinder regeneration from the rat retina ganglioneuron which was mature to the mode which was these OEG human clone cell line middle a parts similar to the first OEG. It is used among the pharmaceutical composition including cell and or the nerve cell damage can be independently repaired in CNS. KEYWORDS The mammal central nervous system (CNS), the axis-cylinder regeneration, and the olfactory sense initial sound cell (OEG)

Reivindicaciones

1. A method of making a population of reverse-immortalised human olfactory ensheathing glia (OEG) cells, which have the ability to promote axonal regeneration from adult CNS neurons, for transplantation into a patient, which comprises: a) providing a sample obtained from primary human OEG cells; b) immortalizing the OEG cells by transforming the OEG cells with a DNA construct comprising a removable DNA segment containing an oncogene or combination of oncogenes, thereby producing immortalised OEG cells; c) growing the immortalised OEG cells; d) selecting those immortalised OEG clonal cell lines which maintain the property of promoting axonal regeneration from adult CNS neurons; and e) removing the oncogene or combination of oncogenes from the immortalised OEG cells, the removal resulting in the production of the population of human OEG cells for transplantation into the patient. 2. The method of claim 1, wherein the oncogene or combination of oncogenes is made removable by flanking it with recombinase target sites, and the removing is accomplished by introducing into the immortalised cells a gene that is expressed to produce a recombinase that specifically recognizes the recombinase target sites. 3. The method of claim 2, wherein the recombinase is Cre recombinase and the recombinase target sites are loxP sites. 4. The method of claim 1, wherein the oncogene is the gene encoding SV40 large T antigen, the gene encoding telomerase catalytic subunit, the gene encoding Bmi-1 protein or any combination of said oncogenes. 5. The method of claim 1, wherein the removable DNA segment further contains a suicide gene, which encodes a gene product that enables destruction of the immortalised cells by an exogenous agent if the removable DNA segment is not removed from the cells. 6. The method of claim 5, wherein the suicide gene is a gene encoding herpes simplex virus thymidine kinase, and the cells are destroyed by exposure to gancyclovir if the removable DNA segment is not removed from the cells. 7. A population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration, producible by the method of claim 1. 8. A population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration, producible by the method of claim 1 for use as a medicament. 9. The use of a population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration, producible by the method of claim 1 for the manufacture of a medicament for the treatment of neural damage wherein the medicament comprises a sufficient quantity of the human OEG cells of claim 7 for transplanting into the patient to provide promotion of neuronal regeneration in the neuronal injured region of the patient. 10. A method of making a population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration from adult CNS neurons, for transplanting into a patient, which comprises: a) providing a sample obtained from primary human OEG cells; b) immortalizing the OEG cells by transforming the OEG cells with a DNA construct comprising a removable DNA segment containing an oncogene or a combination of oncogenes, a selectable marker gene, and a gene encoding herpes simplex virus thymidine kinase, the genes together being flanked on either side by loxP sites; c) growing the immortalised human OEG cells; d) selecting those immortalised OEG clonal cell lines which maintain the property of promoting axonal regeneration from adult CNS neurons; and e) reversing the immortalization of the human OEG cells by removing the DNA segment from the immortalised OEG cells, the removing being accomplished by introducing into the immortalised OEG cells a gene encoding Cre recombinase to effect excision of the DNA segment at the loxP sites, the excision resulting in the production of the population of human OEG cells for transplanting into a patient. 11. The method of claim 10, wherein the oncogene is the gene encoding SV40 large T antigen, the gene encoding telomerase catalytic subunit, the gene encoding Bmi-1 protein or any combination of said oncogenes. 12. A population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration from adult CNS neurons, producible by the method of claim 10. 13. A population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration from adult CNS neurons, producible by the method of claim 10 for use as a medicament. 14. The use of a population of reverse-immortalised human OEG cells, which have the ability to promote axonal regeneration from adult CNS neurons, producible by the method of claim 10 in the manufacture of a medicament for the treatment of neural damage wherein the medicament comprises a sufficient quantity of the OEG cells of claim 12 for transplanting into the patient to provide promotion of neuronal regeneration in the neuronal injured region. 15. A reverse-immortalised human OEG cell, which has the ability to promote axonal regeneration from adult CNS neurons, comprising a primary human OEG cell transformed with a DNA construct comprising two recombinase target sites that flank an oncogene or combination of oncogenes which confers immortalization to the OEG cell, wherein the immortalization is reversible by excision of the DNA construct by cleavage at the recombinase target sites when the target sites are exposed to a recombinase that specifically recognizes the target sites. 16. The reverse-immortalised OEG cell of claim 15, wherein the recombinase target sites are loxP sites and the immortalization is reversible by Cre recombinase cleavage at the loxP sites. 17. The reverse-immortalised OEG cell of claim 15, wherein the DNA construct further comprises a selectable marker gene. 18. The reverse-immortalised OEG cell of claim 15, wherein the DNA construct further comprises a suicide gene, which encodes a gene product that enables destruction of the immortalised OEG cell by an exogenous agent if the oncogene is not removed from the cells. 19. The reverse-immortalised OEG cell of claim 18, wherein the suicide gene is a gene encoding herpes simplex virus thymidine kinase, and the exogenous agent is gancyclovir. 20. A cell line comprising a population of the reverse-immortalised human OEG cells of claim 15. 21. A reverse-immortalised human OEG cell which has the ability to promote axonal regeneration from adult CNS neurons upon transplantation into a patient, producible by exposing the DNA construct within the immortalised human OEG cell of claim 15 to a recombinase that excises the DNA construct by cleavage at the recombinase target sites. 22. A reverse-immortalised human OEG cell which has the ability to promote axonal regeneration from adult CNS neurons upon transplantation into a patient, producible by exposing the DNA construct within the immortalised human OEG cell of claim 15 to a recombinase that excises the DNA construct by cleavage at the recombinase target sites for use as a medicament. 23. The use of a reverse-immortalised human OEG cell which has the ability to promote axonal regeneration from adult CNS neurons upon transplantation into a patient, producible by exposing the DNA construct within the immortalised human OEG cell of claim 15 to a recombinase that excises the DNA construct by cleavage at the recombinase target sites in the manufacture of a medicament for the treatment of neural damage, wherein the medicament comprises a sufficient quantity of the reverse-immortalised OEG human cells of claim 21 for transplanting into the patient to provide promotion of neuronal regeneration in the neuronal injured region of the patient. 24. A cell library comprising a population of reverse-immortalised human OEG cells which have the ability to promote axonal regeneration from adult CNS neurons, producible according to the methods of any one of claims 1 to 6 or 10 to 11. 25. A reverse immortalised human olfactory ensheathing glia (OEG) cell line, which has the ability to promote axonal regeneration from adult CNS neurons comprising a primary human OEG cell transformed with a DNA construct comprising two recombinase target sites that flank an oncogene or combination of oncogenes which confers immortalization to the OEG cell, wherein the immortalization is reversible by excision of the DNA construct by cleavage at the recombinase target sites when the target sites are exposed to a recombinase that specifically recognizes the target sites. 26. A cell line according to claim 25, for use in a method of therapy. 27. A cell line according to claim 25, for use in promoting neuronal regeneration. 28. A pharmaceutical composition comprising a human OEG cell line as defined in claims 25-27, and a pharmaceutically acceptable carrier. 29. The use of reverse-immortalised human olfactory ensheathing glia cells which have the ability to promote axonal regeneration from adult CNS neurons as defined in claims 7, 13, 22 or 25 in the preparation of a medicament for treating neuronal damage.

Etiquetas

Inventores
Moreno Flores MariaMartin Bermejo MariaAvila de Grado JesusWandosell JuradoDiaz Nido JavierLim FilipPastrana Izquierdo ErikaMoreno Flores Maria TeresaGrado Jesus Avila deMartin Bermejo Maria JesusWandosell Jurado FranciscoFlores Maria Teresa MorenoNido Javier DiazIzquierdo Erika PastranaBeermejo Maria Jesus MartinJurado Francisco WandosellBermejo Maria Jesus MartinFilip LimJesus Avila de GradoMaria Teresa Moreno FloresJavier Diaz NidoErika Pastrana IzquierdoMaria Jesus Martin BeermejoFrancisco Wandosell JuradoMaria Jesus Martin BermejoMartin, Beermejo Maria JesusFranci Moreno Flores Maria TerTeresa Moreno Flores MariaJesus Martin Beermejo MariaMoreno Flores Maria Teresa,Martin Beermejo Maria Jesus,Avila de Grado Jesus,Wandosell Jurado Francisco,Diaz Nido Javier,Lim Filip,Pastrana Izquierdo ErikaMartin Beermejo Maria JesusMartin Bermejo Maria JAvila de GradoMoreno Flores, Maria, TeresaMartin Bermejo, MariaMoreno Flores Maria Teresa CenMartin Bermejo Maria Jesus CenMartin Bermejo, Maria, JesusMaria, Teresa Moreno FloresMaria, Jes�S Martin BermejoJes�S Avila de GradoJurado, Francisco WandosellMartin Bermejo Maria JesúsAvila de Grado JesúsFlores Maria Teresa MMartin, Beermejo, Maria, Jesus
Solicitantes
Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridConsejo Superior de Investigaciones Cient�FicasUniversidad Aut�Noma de MadridMoreno Flores Maria TeresaMartin Bermejo Maria JesusAvila de Grado JesusWandosell Jurado FranciscoDiaz Nido JavierLim FilipPastrana Izquierdo ErikaRuffles Graham KeithMartin, Beermejo, Maria, Jesus
Clasificacion ipc
A61K 35/ 30 A IA61P 25/ 00 A IC12N 5/ 0793 A IC12N 5/ 079 A IA61K 48/ 00 A IC12N 15/ 64 A IA61L 27/ 00 A IA61P 43/ 00 A IC12N 15/ 09 A IC12N 5/ 10 A IC12N 5/ 07 A I
Clasificacion cpc
4B024/AA014B024/BA104B024/CA044B024/DA034B024/EA044B024/GA114B024/GA184B024/GA304B065/AA93X4B065/AB014B065/AC204B065/BA014B065/CA444C081/AB184C081/BA124C081/CD344C081/EA014C081/EA024C081/EA114C081/EA134C086/AA014C086/AA024C086/CB074C086/MA014C086/MA044C086/NA144C086/ZA014C086/ZB224C086/ZB264C087/AA014C087/AA024C087/BB334C087/BB454C087/BB634C087/CA044C087/CA124C087/MA674C087/NA144C087/ZA014C087/ZB224C087/ZB26A61K31/522A61K35/30A61L27/00A61L27/00&ZA61L27/38A61L27/38&300A61P25/00A61P35/00A61P43/00&107C12N15/00&AC12N5/00&102C12N5/00&BC12N5/10424/93.21435/366435/368435/455
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