WO2012164137A1 - Cellules mères et cellules de la souche neurale dérivées de la glie olfactive enveloppante, et leurs applications - Google Patents

Cellules mères et cellules de la souche neurale dérivées de la glie olfactive enveloppante, et leurs applications Download PDF

Info

Publication number
WO2012164137A1
WO2012164137A1 PCT/ES2012/070404 ES2012070404W WO2012164137A1 WO 2012164137 A1 WO2012164137 A1 WO 2012164137A1 ES 2012070404 W ES2012070404 W ES 2012070404W WO 2012164137 A1 WO2012164137 A1 WO 2012164137A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
stem cells
neural
glia
olfactory
Prior art date
Application number
PCT/ES2012/070404
Other languages
English (en)
Spanish (es)
Inventor
Cintia MUÑOZ QUILES
Original Assignee
Fundación Investigación En Regeneración Del Sistema Nervioso
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 Fundación Investigación En Regeneración Del Sistema Nervioso filed Critical Fundación Investigación En Regeneración Del Sistema Nervioso
Publication of WO2012164137A1 publication Critical patent/WO2012164137A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0619—Neurons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0623—Stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/08—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from cells of the nervous system

Definitions

  • the invention falls within the technical sector of medical therapies, more specifically in the use of cells and their derivatives in the treatment of diseases and in diagnosis. STATE OF THE PREVIOUS TECHNIQUE
  • Cell transplants constitute a promising therapeutic strategy to repair and / or replace tissues and cells damaged by various skin, cardiac, metabolic, genetic, muscular, etc. pathologies, as well as the nervous system (degenerative, ischemic, trauma diseases, demyelinating, among others) (Revised in (Bjorklund, et al., 2000; Jain, 2009; Reier, 2004)).
  • the host's immune system does not recognize the cells as their own and the patient must receive immunosuppressive medication to avoid implant rejection.
  • the transplanted organs, tissues or cells are compatible with the host's immune system, and such therapy is not needed to avoid rejection.
  • autologous therapy also offers the advantage that the grafted cells or tissue integrate better than when the origin is from another individual or another species. All these advantages have favored that in the field of cell therapy the development of treatments using cells that allow the three options is preferred: auto-, alo- and xeno-transplantation.
  • stem cells allow the availability of cellular phenotypes relevant to human pathology that otherwise could not be obtained from an adult individual.
  • the choice of the type of cell to be transplanted has depended on the type of lesion to be treated and the intrinsic reparative capacity that the cells of choice presented.
  • the purpose of transplanting cells is to achieve the regeneration of the injured axons and that they reestablish the appropriate connections with their targets so that they recover lost functions as a result of aggression.
  • Cells that, spontaneously or after manipulation, produce survival factors and / or axon growth promoters (Ruff, et al., 201 1; Sahni, et al., 201 1; Tetziaff, et al.
  • transplants In the case of degenerative pathologies, the object of cell transplants is twofold. On the one hand, replace the cells that have degenerated, either neurons or glia, with others that can replace their function. On the other hand, transplants should promote the survival of host and transplanted cells, and rescue those cells that have not yet degenerated.
  • a limitation of cellular regenerative therapy in the case of nervous system pathologies is that neurons cannot be obtained from the patient. It is not advisable to perform biopsies of the brain, cerebellum, brain stem, spinal cord or peripheral nervous system to obtain neurons because this would generate additional damage to the patient. In the case of the central nervous system, obtaining glia is also limited for the same reason. In addition, neurons (peripheral and central) and oligodendroglia extracted from the adult nervous system have very low survival and little or no ability to divide, so it would be difficult to obtain a sufficient number of cells for transplantation. To alleviate this problem, stem cells from sources outside the central nervous system are being used to, from them, try to generate the different types of neural lineage.
  • Embryonic stem cells are being used since, because they are pluripotential, they can give rise to neurons and glia (Kim, et al., 2009). For example, they have been used in animals and in stem cell transplants, both embryonic and adult, and oligodendrocyte precursors to promote myelination of naked axons (reviewed in (Mirón, et al., 201 1)). In experimental models of Parkinson's disease, and in some cases in people, stem cells, dopamine neuroblasts, and other dopamine-producing cells (carotid body cells, genetically modified, etc.) have been transplanted (Reviewed in (Fricker-Gates , et al., 201 1)).
  • Transplants of stem cells and their derivatives of neural lineage are also being used to repair other degenerative, traumatic and ischemic diseases of the nervous system (Rodr ⁇ guez, et al., 201 1; Uccelli, et al., 201 1).
  • Several groups are choosing to pre-differentiate the stem cells before being transplanted, towards certain lineages of the neural lineage, such as oligodendroglia, for therapeutic purposes (Sharp, et al., 201 1).
  • the use of embryonic stem cells has important disadvantages. It is difficult to control these cells in vitro without inducing their differentiation towards unwanted and non-neural cell types.
  • embryonic stem cells In addition, in order to obtain a specific phenotype, which is needed for a pathology of the nervous system, embryonic stem cells must undergo several differentiation processes generally through treatment with compounds Chemicals or genetic manipulation. In addition, the use of embryonic stem cells has some controversy regarding the ethical problems derived from using embryos to obtain them. Another drawback is that the cells come from another individual (allotransplant) and therefore are generally rejected by the host. Although this problem could be remedied by performing a "therapeutic cloning", this technique has not been sufficiently developed in humans and there are also ethical conditions as this technique is prohibited in some countries. The safety of embryonic stem cells is also not clear since, being poorly differentiated cells, they have a high risk of generating teratocarcinomas. Even if they have been differentiated before use, they can undergo a process of de-differentiation.
  • the olfactory envelope glia (OEG) or olfactory envelope cells (OEC) constitute a unique cell type that allows the regeneration of axons in the olfactory system of mammals throughout their lives (Ramon-Cueto, et al., 1995). These cells involve the olfactory axons throughout their journey in the peripheral nervous system (SNP) of the olfactory epithelium and the lamina intestinal, and within the central nervous system (CNS) of the olfactory bulb, which constitutes, the latter, somewhat exceptional ( Blanes, 1898; Doucette, 1984; Golgi, 1875; Raisman, 1985).
  • SNP peripheral nervous system
  • CNS central nervous system
  • This innate plasticity of the olfactory envelope glia is what has served as the basis for the present invention, which provides a source of neural stem cells, neurons and glia from these adult and differentiated glial cells of the mammalian nervous system .
  • the first time that OEG cultures were obtained was in 1992 (Ramón-Cueto et al., 1992; Pixley 1992) and since then there are more than 200 scientific publications that, using different culture methods, obtain these same cells well from olfactory bulb (central nervous system, CNS) or nasal cavity (peripheral nervous system, SNP), either of the mucosa or of the laminalitis (Ramón-Cueto et al., 1993; Barnett et al., 1993; Chuah et al., 1993; Alexander et al., 2002; Au et al., 2003; reviewed in Higginson et al., 201 1).
  • Stem cells can be obtained using different compositions of the culture medium.
  • WO 2010/056075 describes a method for obtaining and culturing stem cells that includes ICAM 5, Activin A, decorin, IGFBP7, glypican 3, among other compounds.
  • neural stem cells and precursors of the neuronal lineage are obtained using an inductor containing a compound represented by a general formula.
  • a different method for also obtaining neural stem cells is presented in WO201 1059920.
  • US2008 / 107633 describes a standard definition culture medium, a carbohydrate source, a buffer, a source of hormones, and LIF for generating neuronal stem cells, to stimulate its proliferation and the generation of neuronal and glial cells.
  • US2005 / 0245436 describes a different composition of the culture medium, based on the use of pheromones and luteinizing hormone, to obtain neural stem cells that can be converted into neurons and glial cells.
  • WO 2009/002559 adds LIF and type I collagenase to the culture medium to obtain the neural stem cells, and withdraws LIF for the differentiation of these neural stem cells into neurons and glial cells.
  • Other examples of patent documents that use different culture media to obtain neural stem cells are the following: WO 2008/109320, WO2010 / 052904, WO2010147803. Therefore, one skilled in the art knows that different culture conditions and media can be used to obtain stem cells, neural stem cells and precursors of the neural lineage.
  • Patent documents also emerged that use adult differentiated OEG cultures to obtain OEG cell lines by genetic modification (WO02 / 088337 and WO05 / 012513) or that use differentiated OEG in combination with a pharmacological compound (AU2003 / 249092) .
  • WO02 / 088337 and WO05 / 012513 use differentiated OEG in combination with a pharmacological compound.
  • AU2003 / 249092 a pharmacological compound
  • the neural stem cells object of this invention are obtained from a controlled, already differentiated cell type, which is not multipotential and, in addition, is found both in the peripheral nervous system (SNP) as in the central nervous system (CNS).
  • SNP peripheral nervous system
  • CNS central nervous system
  • neural stem cells obtained from a controlled, already differentiated cell type that is not multipotential and that is also found in both the peripheral nervous system (SNP) and the central nervous system ( SNC).
  • SNP peripheral nervous system
  • SNC central nervous system
  • DESCRIPTION OF THE INVENTION It is desirable to have a source of neurons and glia, from differentiated cells of the nervous system, from cells of the neural line in which there is no multipotentiality (to avoid the risk of tumor formation), which It can be obtained from adults to guarantee an autologous therapy, and that the source of these differentiated cells is located both in the peripheral and central nervous system, in order to offer the possibility of obtaining the neurons and glia of both systems.
  • the present invention allows, for the first time, to obtain cells of the neural lineage (neurons, glia, others) from adult differentiated cells also of the neural lineage that are found both in the peripheral nervous system and in the central nervous system, for the disease therapy, for diagnosis and for the evaluation of the biological activity of various agents.
  • the nervous structures that are used for the generation of The cells object of the invention are accessible structures whose elimination or biopsy does not cause negative sequelae.
  • a first aspect of the invention consists in the generation of neural stem cells and neural progenitors derived from dedifferentiated olfactory envelope glia.
  • the olfactory enveloping glia is preferably obtained from the olfactory bulb (central nervous system), as it is of special relevance for pathologies of the central nervous system (CNS) because both the origin and derived cells will be from the CNS, without this excluding their obtaining of the olfactory mucosa and lamina intestinal (peripheral nervous system). That is, the envelope glia to generate neural stem cells and progenitors of the neural lineage can be obtained from both the olfactory mucosa (including the lamina intestinal) and the olfactory bulb. Both the olfactory bulb and the olfactory mucosa are surgically accessible nerve structures and whose biopsy or extraction causes minimal risks to patients.
  • a second aspect of the invention consists in obtaining in vitro different cell types from the neural lineage (neurons, glia, others), without these cell types being exclusive of others, originating from the stem cells and the precursors derived from the surrounding glia. -differentiated.
  • a third aspect of the invention is the use of all these cells derived from the olfactory envelope glia, to generate others by their genetic modification or manipulation of any kind.
  • a fourth aspect of the invention consists in the use of any of the cells derived from the olfactory envelope glia mentioned previously, and / or the products or molecules derived therefrom, in the treatment of pathologies or diseases.
  • a fifth aspect of the invention consists in the use of any of the cells derived from the olfactory envelope glia mentioned above, and / or the products or molecules derived therefrom, in the preparation of pharmacological compounds or medicaments that can be used for regeneration. of organs and tissues or for the treatment of diseases and pathologies. Another aspect of this invention is these compounds or medicaments mentioned.
  • a sixth aspect of the invention consists in the use of any of the cells derived from the olfactory envelope glia mentioned previously, and / or the products or molecules derived therefrom, for the evaluation of the biological activity of different agents (compounds, cells, gene expression products, molecules, drugs, or others) both in vitro and in vivo.
  • a seventh aspect of the invention consists in the use of any of the cells derived from the olfactory envelope glia mentioned previously, and / or the products or molecules derived therefrom, in the design or conduct of diagnostic tests.
  • the present invention relates to stem cells and neural lineage cells all derived from olfactory envelope glia, and their use.
  • Stem cells and neural types obtained from the adult enveloping glia can be used for the treatment of various pathologies of the nervous system.
  • These cells and / or their derived molecules may be used either alone or in combination with others.
  • therapeutic strategies of various kinds transplants of other cells, gene therapy, administration of compounds, etc).
  • the present invention relates to cells consisting of stem cells and precursors obtained from olfactory glia or OEG or GEO (also called olfactory envelope cells or OEC).
  • the present invention relates to cells comprising various cell lineages (neurons, glia or others) generated from olfactory envelope glia (OEG) and / or derived from stem cells obtained from olfactory envelope glia.
  • various cell lineages neurons, glia or others
  • OEG olfactory envelope glia
  • stem cells obtained from olfactory envelope glia.
  • the present invention relates to the use of stem cells and the different cell types (neurons, glia, others) generated from the olfactory glia, or any molecule or molecules that these cells produce, for the treatment of diseases and lesions of the nervous system of mammals, including humans, as well as to treat any other pathology in which these cells may be useful.
  • the present invention relates to the combination of stem cell transplants and / or the different cell types (neurons, glia, others) generated from the olfactory envelope glia, with another or other therapeutic strategy / s for the treatment of diseases and injuries of the nervous system of mammals, including humans, as well as to treat any other pathology in which these combinations may be useful.
  • the present invention relates to the new cell lines or cell types that are obtained after genetic or other manipulation of the stem cells and the different cell types (neurons, glia, others) generated from the olfactory envelope glia or derivatives her.
  • the present invention relates to the new molecules produced by the stem cells and / or the different cell types (neurons, glia, others) generated from the olfactory envelope glia or derivatives thereof, which have biological activity, as well as the molecules known in which a new biological effect or activity is described. Also the use of these substances as pharmacological targets or for the development of new products for diagnostic, therapeutic or other purposes.
  • the present invention relates to drugs or drugs that are designed to enhance the effect of the new or known molecules identified, produced by the stem cells and / or the different cell types (neurons, glia, others) generated from the glia olfactory envelope or derivatives thereof.
  • the present invention relates to the use of stem cells and the different cell types (neurons, glia, others) generated from the olfactory envelope glia or derivatives thereof, or the use of any molecule or molecules that these cells produce, to perform in vitro tests that allow testing of new compounds, and for the search and development of new therapeutic agents.
  • the present invention relates to the use of stem cells and the different cell types (neurons, glia, others) generated from the olfactory envelope glia or derivatives thereof, to conduct genomic studies of pathologies, and also pharmacogenomics, where The activity of a compound that is used in the nervous system could be related to the gene structure of the individual.
  • the present invention relates to the use of stem cells and the different cell types (neurons, glia, others) generated from the olfactory glia or derivatives thereof, or use of any cell obtained by modification thereof (genetics). or others), or of any molecule or molecules that these cells produce, in obtaining tissues and organs.
  • the present invention relates to the use of the stem cells and the different cell types (neurons, glia, others) generated from the olfactory envelope glia or derivatives thereof, or from any cell obtained by modification thereof (genetics or others), or the use of any molecule or molecules that these cells produce, in combination with other cells, compounds or pharmacological products for all purposes set forth in the previous points.
  • FIGURE 1A shows the appearance of an olfactory envelope glia culture before stem cells and precursors are obtained.
  • Figure 1 B shows the aspect of olfactory envelope glia culture 3 days after the culture medium that produces its differentiation and the generation of stem cells and precursor cells has been administered.
  • Figures 1 C and 1 D show the spheres formed of stem cells and precursors, which are obtained from olfactory envelope glia cultures after the culture medium that favors their differentiation has been administered.
  • FIGURE 2 shows the same sphere that contains stem cells and precursors but displayed differently.
  • Figure 2A shows the sphere in clear field.
  • Figure 2B shows that stem cells and precursors that are contained in the spheres are viable since they all contain the vital dye (CSFE).
  • Figure 2C shows that the cells contained in the spheres are dividing, since they have captured the BrdU proliferation marker.
  • Figure 3 shows the cell types contained in the spheres obtained from olfactory envelope glia after dedifferentiation, by means of marking for different molecules. This staining was performed after 8 days in vitro.
  • Figures 3A and 3B show that in the same spheres there are precursors of neurons ( ⁇ -111-tubulin positive cells) (A) and neural stem cells (nestin positive) (B).
  • Figures 3C and 3D show that in the same spheres there are cells expressing p75, which is a marker of neuronal precursors (C) and glial cells (labeled with anti-GFAP) (D).
  • Figure 4 shows the cell types obtained after differentiating the differentiated envelope glia (after differentiating the spheres). This staining was performed after keeping the cells 7 days in the differentiation culture medium.
  • Figures 4A and 4B show that after differentiating the de-differentiated envelope glia, glial line cells that are not olfactory envelope glia (positive cells against GFAP and negative cells against p75) are obtained and olfactory envelope glia is also re-obtained ( GFAP and p75 positive).
  • Figures 4C and 4D show that after differentiating the differentiated envelope glia, neurons (C) and glia (D) are obtained. ). Neurons are identified with ⁇ - ⁇ -tubulin (Tuj) (C), and the glia with GFAP (D). The images are taken in a confocal microscope and show the same field of culture.
  • Figure 4E shows the same field of culture of Figures C and D, in which we have analyzed in the confocal microscope if there is co-localization of both markers in the same cells.
  • EXAMPLE 1 Obtaining cell spheres from olfactory envelope glia
  • Adult OEG cultures are obtained from adult olfactory bulbs as previously described (Munoz-Quiles, et al., 2009; Ramon-Cueto, et al., 2000; Ramon-Cueto, et al., 1994; Rubio, et al., 2008).
  • the OEG is maintained in sterile culture medium (DMEM, Dulbecco Modifier Eagle's Medium and F12) containing 2mM L glutamine, antibiotics and 10% fetal bovine serum.
  • DMEM Dulbecco Modifier Eagle's Medium and F12
  • the serum that is used to supplement the medium can be human and thus be used from an autologous source.
  • the medium used to obtain stem cell spheres from OEG is composed of Neurobasal, B27 (2%), L-Glutamine (200mM), Human Epidermal Growth Factor (Hu EGF) (100pg / mL) and Factor of growth of beta fibroblasts (FGF ⁇ ) (100pg / mL).
  • the cultures are kept in an incubator with 5% CO2 at 37 ° C. Half of these cultures are changed every 2-3 days. After three days the first spheres begin to be seen and they increase in size by dividing the cells that compose them progressively. ( Figure 1 ).
  • Immunocytochemical characterization of cells contained in the spheres Neurospheres are very dynamic cellular structures with different gradients of cell proliferation, survival, apoptosis and phagocytosis and contain progenitors of different cell types in different states of differentiation (Ahmed, 2009).
  • immunocytochemicals are performed using antibodies against Nestine, ⁇ - ⁇ -tubulin (Tuj), acidic protein of the glial filaments (GFAP) and the low affinity receptor of nerve growth factor or p75. This last molecule has been identified in both neuroblasts and neural stem cells. Neural stem cells coexpress p75 and nestin, while neuronal line cells co-express p75 with Tuj.
  • the spheres obtained from olfactory envelope glia cultures contain cells of various types: neural stem cells and neuronal and glial progenitors.
  • the presence of nestin and p75 positive cells indicates that the spheres contain neural stem cells.
  • the presence of positive ⁇ -)-tubulin (Tuj) and positive cells against p75 indicates that the spheres contain neuronal precursors.
  • the presence of some positive GFAP cells that are negative for the other markers indicates that there are glial line cells in the spheres.
  • These glial cells are not olfactory envelope glia since GFAP and p75 do not colocalize in the same cells (compare Figure 2C and 2D) and the olfactory envelope glia expresses both molecules. (Figure 3).
  • EXAMPLE 3 Obtaining neurons and glia from spheres generated with olfactory envelope glia cultures
  • the spheres are transferred to new glass plates pre-treated with Poly-L-Lysine (25 pg / mL; 2h) and Laminin (10 pL / mL; 4h).
  • the culture medium used for the differentiation of spheres in neurons and glia is Neurobasal, B27 (2%), L-Glutamine (200mM), without EGF or FGF. Said medium is changed every 2-3 days and the cultures are maintained at 37 ° C and 5% CO2.
  • the cells have adhered to the substrate, differentiate and distribute forming colonies. After 7-8 days in culture, the cells are fixed with 4% paraformaldehyde and their phenotypes are characterized by immunocytochemistry using antibodies against GFAP, p75, ⁇ -lll-tubulin and 04.
  • ⁇ -lll-tubulin After 8 days in the culture medium described, approximately 45% of the cells express ⁇ -lll-tubulin, which demonstrates a differentiation of the cells from the spheres to neurons. 69% cells express GFAP, demonstrating differentiation to glial line cells. GFAP is also a marker of precursors of certain types of neurons, so that the cells that express both, ⁇ - ⁇ -tubulin and GFAP, are of neuronal lineage, while those that express only GFAP are of glial lineage. 56% of cells express 04, a marker of oligodendroglia precursors. The cells expressing only 04 demonstrate that the cells of the spheres have differentiated towards oligodendroglia. A small percentage of cells express 04 and also GFAP, which demonstrates their re-differentiation to olfactory envelope glia ( Figure 4).
  • OECs olfactory ensheathing cells
  • Enshathing glia transplants promote dorsal root regeneration after spinal reflex restitution after multiple lumbar rhizotomy. Ann. Neurol 45, 207-215.
  • the olfactory nerve contains two populations of glia identified both in vitro and in vivo. Glia 5, 269-284.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biotechnology (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Cell Biology (AREA)
  • Neurosurgery (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne l'obtention de cellules mères et de cellules de souche neurale (neurones, glie, autres) à partir de la glie olfactive enveloppante (OEG ou GEO, aussi appelées cellules olfactives enveloppantes ou OEC), les cellules ainsi obtenues et leurs applications. Plus concrètement, l'invention concerne des cellules mères et les précurseurs de souche neurale (ou autres) dérivés de la dédifférenciation cellulaire de la glie olfactive enveloppante, qui peuvent être différenciés et donner lieu à divers types cellulaires, généralement de la souche neurale, sans être exclusifs. L'invention concerne également l'application des cellules mères et des différentes lignées cellulaires obtenues à partir de la glie olfactive enveloppante, et les produits dérivés de tous les types cellulaires générés, dans le traitement de maladies, en thérapie cellulaire, dans la recherche et la conception de nouveaux médicaments et dans des études cellulaires, moléculaires et de génomique et pharmacogénomique de pathologies humaines.
PCT/ES2012/070404 2011-05-30 2012-05-30 Cellules mères et cellules de la souche neurale dérivées de la glie olfactive enveloppante, et leurs applications WO2012164137A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP201100630 2011-05-30
ES201100630 2011-05-30

Publications (1)

Publication Number Publication Date
WO2012164137A1 true WO2012164137A1 (fr) 2012-12-06

Family

ID=46513782

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2012/070404 WO2012164137A1 (fr) 2011-05-30 2012-05-30 Cellules mères et cellules de la souche neurale dérivées de la glie olfactive enveloppante, et leurs applications

Country Status (1)

Country Link
WO (1) WO2012164137A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105349491A (zh) * 2015-12-15 2016-02-24 黄红云 来源于嗅粘膜神经元细胞分离制备技术
US11959100B2 (en) 2017-11-30 2024-04-16 Kyoto University Method for culture of cells

Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001030982A1 (fr) 1999-10-27 2001-05-03 Griffith University Cellules d'engainement olfactive isolees a partir de la lamina propria
WO2002088337A1 (fr) 2001-04-19 2002-11-07 Consejo Superior De Investigaciones Científicas Nevroglie olfactive enveloppante immortalisee par l'introduction d'une telomerase
WO2003064601A2 (fr) 2002-01-28 2003-08-07 University Of Louisville Research Foundation, Inc. Cellules souches olfactives humaines
AU2003249092A1 (en) 2002-08-07 2004-02-25 Medical Research Council Olfactory ensheathing cells (oecs) in an extracellular matrix for use in axon regeneration
WO2005012513A1 (fr) 2003-07-18 2005-02-10 Consejo Superior De Investigaciones Cientificas Nevroglies enveloppantes olfactives immortalisees de maniere reversible et leur utilisation dans la promotion de la regeneration neuronale
US20050245436A1 (en) 2004-02-13 2005-11-03 Stem Cell Therapeutics Corp. Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis
WO2007020611A2 (fr) 2005-08-19 2007-02-22 ECBIO - Investigação e Desenvolvimento em Biotecnologia, S.A. Cellules souches/progenitrices neurales humaines adultes provenant de l'epithelium olfactif et de la lamina propria olfactive, procede d'isolement, proliferation et differenciation dans un milieu de culture sans serum et utilisation pour la transplantation
WO2007069927A2 (fr) 2005-12-14 2007-06-21 Akademia Medyczna Im. Piastow Slaskich Méthodes pour obtenir des cellules gliales olfactives et leur application
US20070141035A1 (en) 2005-12-16 2007-06-21 Hung Li Pluripotent olfactory stem cells
US20080107633A1 (en) 1997-09-05 2008-05-08 Melissa Carpenter Cultures of human CNS neural stem cells
WO2008109320A1 (fr) 2007-03-08 2008-09-12 Sekula Raymond F Jr Procédé de production de cellules souches neurales purifiées et procédés apparentés de traitement d'un patient
WO2009002559A1 (fr) 2007-06-27 2008-12-31 President And Fellows Of Harvard College Cellules souches neurales
CN101591642A (zh) 2008-05-30 2009-12-02 北京市虹天济神经科学研究院 两嗅细胞共培诱导嗅干细胞增殖和分化的方法
WO2010051531A1 (fr) 2008-10-31 2010-05-06 University Of Louisville Reserch Foundation, Inc. Cellules souches dérivées de l'épithélium olfactif et procédés pour leur utilisation
WO2010052904A1 (fr) 2008-11-05 2010-05-14 Keio University Méthode de production de cellules souches neurales
WO2010056075A2 (fr) 2008-11-14 2010-05-20 Medipost Co., Ltd Composition comprenant des cellules souches mésenchymateuses ou une solution de culture de cellules souches mesenchymateuses pour la prevention et le traitement de maladies neurales
WO2010077294A1 (fr) 2008-12-09 2010-07-08 King Faisal Specialist Hospital & Research Centre Cellules souches olfactives et leurs utilisations
WO2010147803A2 (fr) 2009-06-08 2010-12-23 Regents Of The University Of Michigan Cellules souches neurales issues de cervelet adulte et compositions et procédés pour produire des oligodendrocytes
WO2011059920A2 (fr) 2009-11-10 2011-05-19 The J. David Gladstone Institutes Procédés de génération de cellules souches neuronales
WO2011062013A1 (fr) 2009-11-18 2011-05-26 国立大学法人徳島大学 Inducteur de différenciation sélective en cellules souches neurales et/ou en cellules précurseurs neurales

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080107633A1 (en) 1997-09-05 2008-05-08 Melissa Carpenter Cultures of human CNS neural stem cells
WO2001030982A1 (fr) 1999-10-27 2001-05-03 Griffith University Cellules d'engainement olfactive isolees a partir de la lamina propria
WO2002088337A1 (fr) 2001-04-19 2002-11-07 Consejo Superior De Investigaciones Científicas Nevroglie olfactive enveloppante immortalisee par l'introduction d'une telomerase
WO2003064601A2 (fr) 2002-01-28 2003-08-07 University Of Louisville Research Foundation, Inc. Cellules souches olfactives humaines
AU2003249092A1 (en) 2002-08-07 2004-02-25 Medical Research Council Olfactory ensheathing cells (oecs) in an extracellular matrix for use in axon regeneration
WO2005012513A1 (fr) 2003-07-18 2005-02-10 Consejo Superior De Investigaciones Cientificas Nevroglies enveloppantes olfactives immortalisees de maniere reversible et leur utilisation dans la promotion de la regeneration neuronale
US20050245436A1 (en) 2004-02-13 2005-11-03 Stem Cell Therapeutics Corp. Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis
WO2007020611A2 (fr) 2005-08-19 2007-02-22 ECBIO - Investigação e Desenvolvimento em Biotecnologia, S.A. Cellules souches/progenitrices neurales humaines adultes provenant de l'epithelium olfactif et de la lamina propria olfactive, procede d'isolement, proliferation et differenciation dans un milieu de culture sans serum et utilisation pour la transplantation
WO2007069927A2 (fr) 2005-12-14 2007-06-21 Akademia Medyczna Im. Piastow Slaskich Méthodes pour obtenir des cellules gliales olfactives et leur application
US20070141035A1 (en) 2005-12-16 2007-06-21 Hung Li Pluripotent olfactory stem cells
WO2008109320A1 (fr) 2007-03-08 2008-09-12 Sekula Raymond F Jr Procédé de production de cellules souches neurales purifiées et procédés apparentés de traitement d'un patient
WO2009002559A1 (fr) 2007-06-27 2008-12-31 President And Fellows Of Harvard College Cellules souches neurales
CN101591642A (zh) 2008-05-30 2009-12-02 北京市虹天济神经科学研究院 两嗅细胞共培诱导嗅干细胞增殖和分化的方法
WO2010051531A1 (fr) 2008-10-31 2010-05-06 University Of Louisville Reserch Foundation, Inc. Cellules souches dérivées de l'épithélium olfactif et procédés pour leur utilisation
WO2010052904A1 (fr) 2008-11-05 2010-05-14 Keio University Méthode de production de cellules souches neurales
WO2010056075A2 (fr) 2008-11-14 2010-05-20 Medipost Co., Ltd Composition comprenant des cellules souches mésenchymateuses ou une solution de culture de cellules souches mesenchymateuses pour la prevention et le traitement de maladies neurales
WO2010077294A1 (fr) 2008-12-09 2010-07-08 King Faisal Specialist Hospital & Research Centre Cellules souches olfactives et leurs utilisations
WO2010147803A2 (fr) 2009-06-08 2010-12-23 Regents Of The University Of Michigan Cellules souches neurales issues de cervelet adulte et compositions et procédés pour produire des oligodendrocytes
WO2011059920A2 (fr) 2009-11-10 2011-05-19 The J. David Gladstone Institutes Procédés de génération de cellules souches neuronales
WO2011062013A1 (fr) 2009-11-18 2011-05-26 国立大学法人徳島大学 Inducteur de différenciation sélective en cellules souches neurales et/ou en cellules précurseurs neurales

Non-Patent Citations (47)

* Cited by examiner, † Cited by third party
Title
AHMED, S: "The culture of neural stem cells", JOURNAL OF CELLULAR BIOCHEMISTRY, vol. 106, 2009, pages 1 - 6
ALEXANDER, CL; FITZGERALD, UF; BARNETT, SC: "Identification of growth factors that promote long-term proliferation of olfactory ensheathing cells and modulate their antigenic phenotype", GLIA, vol. 37, 2002, pages 349 - 364
AU, E; ROSKAMS, AJ: "Olfactory ensheathing cells of the lamina propria in vivo and in vitro", GLIA, vol. 41, 2003, pages 224 - 236, XP055039797, DOI: doi:10.1002/glia.10160
B. MURDOCH ET AL: "A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons", JOURNAL OF NEUROSCIENCE, vol. 28, no. 16, 16 April 2008 (2008-04-16), pages 4271 - 4282, XP055035704, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.5566-07.2008 *
BARNETT, SC; HUTCHINS, AM; NOBLE, M: "Purification of olfactory nerve ensheathing cells from the olfactory bulb", DEV. BIOL., vol. 55, 1993, pages 337 - 350, XP024779539, DOI: doi:10.1006/dbio.1993.1033
BJORKLUND, A; LINDVALL, 0: "Cell replacement therapies for central nervous system disorders", NATURE NEUROSCIENCE, vol. 3, 2000, pages 537 - 544, XP002524953, DOI: doi:10.1038/75705
BLANES, T: "Sobre algunos puntos dudosos de la estructura del bulbo olfatorio", REV TRIM MICROGRAF, vol. 3, 1898, pages 99 - 127
CHUAH, MI; AU, C: "Cultures of ensheathing cells from neonatal rats olfactory bulbs", BRAIN RES., vol. 601, 1993, pages 213 - 220
DOUCETTE, JR: "The glial cells in the nerve fiber layer of the rat olfactory bulb", ANAT REC, vol. 210, 1984, pages 385 - 391
FRICKER-GATES; RA,GATES, MA: "Stem cell-derived dopamine neurons for brain repair in Parkinson's disease", REGENERATIVE MEDICINE, vol. 5, 2011, pages 267 - 278
GOLGI, C: "Sulla fina anatomia del bulbi olfatorii", REGGIO-EMILIA
HIGGINSON, JR; BARNETT, SC: "The culture of olfactory ensheathing cells (OECs)-a distinct glial cell type", EXP. NEUROL., vol. 229, 2011, pages 2 - 9
JAIN, KK: "Cell therapy for CNS trauma", MOLECULAR BIOTECHNOLOGY, vol. 42, 2009, pages 367 - 376, XP055090340, DOI: doi:10.1007/s12033-009-9166-8
KIM, SU; DE VELLIS, J: "Stem cell-based cell therapy in neurological diseases: a review", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 87, 2009, pages 2183 - 2200, XP002561476
LI, Y; FIELD, PM; RAISMAN, G: "Regeneration of adult rat corticospinal axons induced by transplanted olfactory ensheathing cells", J. NEUROSCI., vol. 18, 1998, pages 10514 - 10524, XP002954081
LU JIKE ET AL: "Olfactory ensheathing cells: Their potential use for repairing the injured spinal cord", SPINE, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 27, no. 8, 15 April 2002 (2002-04-15), pages 887 - 892, XP009162042, ISSN: 0362-2436 *
MACKAY-SIM, A; ST JOHN, JA: "Olfactory ensheathing cells from the nose: Clinical application in human spinal cord injuries", EXP NEUROL, vol. 229, 2011, pages 174 - 180
MIRON, VE; KUHLMANN, T; ANTEL, JP: "Cells of the oligodendroglial lineage, myelination, and remyelination", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1812, 2011, pages 184 - 193, XP027561296
MUNOZ-QUILES, C; SANTOS-BENITO, FF; LLAMUSI, MB; RAMON-CUETO, A: "Chronic spinal injury repair by olfactory bulb ensheathing glia and feasibility for autologous therapy", J NEUROPATHOL EXP NEUROL, vol. 68, 2009, pages 1294 - 1308
NAVARRO, X; VALERO, A; GUDINO, G; FLORES, J; RODRIGUEZ, FJ; VERDU, E; PASCUAL, R; CUADRAS, J; NIETO-SAMPEDRO, M: "Enshathing glia transplants promote dorsal root regeneration after spinal reflex restitution after multiple lumbar rhizotomy", ANN. NEUROL., vol. 45, 1999, pages 207 - 215, XP009023549, DOI: doi:10.1002/1531-8249(199902)45:2<207::AID-ANA11>3.0.CO;2-K
PAGANO S F ET AL: "ISOLATION AND CHARACTERIZATION OF NEURAL STEM CELLS FROM THE ADULT HUMAN OLFACTORY BULB", STEM CELLS, ALPHAMED PRESS, DAYTON, OH, US, vol. 18, no. 4, 1 August 2000 (2000-08-01), pages 295 - 300, XP001000805, ISSN: 1066-5099, DOI: 10.1634/STEMCELLS.18-4-295 *
PIXLEY, S: "The olfactory nerve contains two populations of glia identified both in vitro e in vivo", GLIA, vol. 5, 1992, pages 269 - 284
RAISMAN, G: "Specialized neuroglial arrangement may explain the capacity of vomeronasal axons to reinnervate central neurons", NEUROSCIENCE, vol. 14, 1985, pages 237 - 254, XP024368144, DOI: doi:10.1016/0306-4522(85)90176-9
RAM6N-CUETO, A; NIETO-SAMPEDRO, M: "Glial cells from the adult rat olfactory bulb, immunocytochemical properties of pure cultures of ensheathing cells", NEUROSCI, vol. 47, 1992, pages 213 - 220, XP024384605, DOI: doi:10.1016/0306-4522(92)90134-N
RAM6N-CUETO, A; PEREZ, J; NIETO-SAMPEDRO, M: "In vitro enfolding of olfactory neurites by p75NGF receptor positive ensheathing cells from adult rat olfactory bulb", EUR. J. NEUROSCI., vol. 5, 1993, pages 1172 - 1180
RAMON-CUETO, A; CORDERO, MI; SANTOS-BENITO, FF; AVILA, J: "Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia", NEURON, vol. 25, 2000, pages 425 - 435, XP002657833, DOI: doi:10.1016/s0896-6273(00)80905-8
RAMON-CUETO, A; MUNOZ-QUILES, C: "Clinical application of adult olfactory bulb ensheathing glia for nervous system repair", EXP NEUROL, vol. 229, 2011, pages 181 - 194
RAMON-CUETO, A; NIETO-SAMPEDRO, M: "Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants", EXP NEUROL, vol. 127, 1994, pages 232 - 244
RAMON-CUETO, A; VALVERDE, F: "Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties", GLIA, vol. 14, 1995, pages 163 - 173, XP009084061, DOI: doi:10.1002/glia.440140302
REEKMANS, K; PRAET, J; DAANS, J; REUMERS, V; PAUWELS, P; VAN DER LINDEN, A; BERNEMAN, ZN; PONSAERTS, P: "Current Challenges for the Advancement of Neural Stem Cell Biology and Transplantation Research", STEM CELL REVIEWS, 2011
REIER, PJ: "Cellular Transplantation Strategies for Spinal Cord Injury and Translational Neurobiology", NEURORX, vol. 1, 2004, pages 424 - 451, XP005871830, DOI: doi:10.1602/neurorx.1.4.424
RODRIGUEZ, FD; VECINO, E: "Stem cell plasticity, neuroprotection and regeneration in human eye diseases", CURRENT STEM CELL RESEARCH & THERAPY, vol. 6, 2011, pages 73 - 81
ROISEN F J ET AL: "ADULT HUMAN OLFACTORY STEM CELLS", BRAIN RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 890, no. 1, 26 January 2001 (2001-01-26), pages 11 - 22, XP001000797, ISSN: 0006-8993, DOI: 10.1016/S0006-8993(00)03016-X *
RUBIO, MP; MUNOZ-QUILES, C; RAMON-CUETO, A: "Adult olfactory bulbs from primates provide reliable ensheathing glia for cell therapy", GLIA, vol. 56, 2008, pages 539 - 551
RUFF, CA; WILCOX, JT; FEHLINGS, MG: "Cell-based transplantation strategies to promote plasticity following spinal cord injury", EXP. NEUROL., 2011
SAHNI, V; KESSLER, JA: "Stem cell therapies for spinal cord injury", NAT REV NEUROL, vol. 6, 2011, pages 363 - 372, XP055188825, DOI: doi:10.1038/nrneurol.2010.73
SASAKI, M; LANKFORD, KL; RADTKE, C; HONMOU, O; KOCSIS, JD: "Remyelination after olfactory ensheathing cell transplantation into diverse demyelinating environments", EXP NEUROL, vol. 229, 2011, pages 88 - 98, XP028480600, DOI: doi:10.1016/j.expneurol.2011.01.010
SHARP, J; FRAME, J; SIEGENTHALER, M; NISTOR, G; KEIRSTEAD, HS: "Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury", STEM CELLS (DAYTON, OHIO, vol. 28, 2011, pages 152 - 163
STAGG, J: "Mesenchymal stem cells in cancer", STEM CELL REVIEWS, vol. 4, 2008, pages 119 - 124
TETZLAFF, W; OKON, EB; KARIMI-ABDOLREZAEE, S; HILL, CE; SPARLING, JS; PLEMEL, JR; PLUNET, WT; TSAI, EC; BAPTISTE, D; SMITHSON, LJ: "A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury", JOURNAL OF NEUROTRAUMA, 2011
UCCELLI, A; MANCARDI, G: "Stem cell transplantation in multiple sclerosis", CURRENT OPINION IN NEUROLOGY, vol. 23, 2011, pages 218 - 225
VEGA GARCÍA-ESCUDERO ET AL: "A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth", CELL TRANSPLANTATION, vol. 20, no. 2, 1 February 2011 (2011-02-01), pages 153 - 166, XP055035706, ISSN: 0963-6897, DOI: 10.3727/096368910X522108 *
WETZIG, A; MACKAY-SIM, A; MURRELL, W: "Characterization of olfactory stem cells", CELL TRANSPLANTATION, 2011
WORTHLEY, DL; RUSZKIEWICZ, A; DAVIES, R; MOORE, S; NIVISON-SMITH, I; BIK TO, L; BROWETT, P; WESTERN, R; DURRANT, S, SO, J; YOUNG,: "Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation", STEM CELLS (DAYTON, OHIO, vol. 27, 2009, pages 1463 - 1468
WRIGHT, KT; EI MASRI, W; OSMAN, A; CHOWDHURY, J; JOHNSON, WE: "Bone Marrow for the Treatment of Spinal Cord Injury: Mechanisms and Clinical Application", STEM CELLS (DAYTON, OHIO, vol. 29, 2011, pages 10
XU X M ET AL: "Transplantation-mediated strategies to promote axonal regeneration following spinal cord injury", RESPIRATORY PHYSIOLOGY AND NEUROBIOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 169, no. 2, 30 November 2009 (2009-11-30), pages 171 - 182, XP026733935, ISSN: 1569-9048, [retrieved on 20090807], DOI: 10.1016/J.RESP.2009.07.016 *
ZHU, W; XU, W; JIANG, R; QIAN, H; CHEN, M; HU, J; CAO, W; HAN, C; CHEN, Y: "Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo", EXPERIMENTAL AND MOLECULAR PATHOLOGY, vol. 80, 2006, pages 267 - 274, XP024944837, DOI: doi:10.1016/j.yexmp.2005.07.004

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105349491A (zh) * 2015-12-15 2016-02-24 黄红云 来源于嗅粘膜神经元细胞分离制备技术
CN105349491B (zh) * 2015-12-15 2019-09-24 北京市虹天济神经科学研究院 来源于嗅粘膜神经元细胞分离制备技术
US11959100B2 (en) 2017-11-30 2024-04-16 Kyoto University Method for culture of cells

Similar Documents

Publication Publication Date Title
Parmar et al. The future of stem cell therapies for Parkinson disease
Song et al. Stem cells: a promising candidate to treat neurological disorders
Jensen et al. Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model
Ma et al. Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice
Pouya et al. Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination
Su et al. Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord
Casarosa et al. Neural stem cells: ready for therapeutic applications?
Erceg et al. Human embryonic stem cell differentiation toward regional specific neural precursors
Kim Genetically engineered human neural stem cells for brain repair in neurological diseases
Marshall et al. The therapeutic potential of human olfactory-derived stem cells
Sun et al. Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury
Czekaj et al. In vitro expanded stem cells from the developing retina fail to generate photoreceptors but differentiate into myelinating oligodendrocytes
Willerth Engineering neural tissue from stem cells
Peng et al. Survival and engraftment of dopaminergic neurons manufactured by a Good Manufacturing Practice-compatible process
Ren et al. Expansion of murine and human olfactory epithelium/mucosa colonies and generation of mature olfactory sensory neurons under chemically defined conditions
JP2020522522A (ja) 網膜疾患を処置するための組成物ならびにそれを作製および使用するための方法
Oz et al. Neural stem cells for Parkinson’s disease management: Challenges, nanobased support, and prospects
Takahashi Stem cell therapy for Parkinson’s disease
Sandquist et al. Stem cells, bioengineering, and 3-D scaffolds for nervous system repair and regeneration
KR102236642B1 (ko) 편도 유래 중간엽 줄기세포로부터 운동신경세포의 분화방법
WO2012164137A1 (fr) Cellules mères et cellules de la souche neurale dérivées de la glie olfactive enveloppante, et leurs applications
He et al. The aOECs facilitate the neuronal differentiation of neural stem cells in the inflammatory microenvironment through up-regulation of bioactive factors and activation of Wnt3/β-Catenin Pathway
KR20200026984A (ko) 랜드마크 전사 인자를 사용한 줄기 세포 분화에 의한 신경 전구 세포, 핍지교세포 전구 세포, 및 핍지교세포의 유도
Ng et al. Prospects of stem cells for retinal diseases
Bianco et al. Rapid serum-free isolation of oligodendrocyte progenitor cells from adult rat spinal cord

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12735313

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC

122 Ep: pct application non-entry in european phase

Ref document number: 12735313

Country of ref document: EP

Kind code of ref document: A1