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Title:
METHOD FOR PREPARING OLIGODENDROCYTES AND USE
Document Type and Number:
WIPO Patent Application WO/2023/165062
Kind Code:
A1
Abstract:
Provided are a method for preparing oligodendrocytes and use. According to the solution provided, the major steps of oligodendrocyte differentiation is replayed in a time significantly shorter than 75-95 days which are required for previous solutions. The cannabinoid receptor agonist WIN55212-2 is used to induce NSC differentiation, promoting OLIG2 + OPC induction. WIN-derived OLIG2 + progenitor cells differentiate into PDGFRα + OPCs, which have high mobility and can further differentiate into mature OLs with a powerful myelination ability. When WIN-derived OPCs are transplanted to lesions, the mobility of mice with spinal cord injury (SCI) begins to improve significantly the second week after the transplantation. The results of immunostaining show that WIN-derived OPCs can differentiate into mature OLs, causing myelination of damaged axons.

Inventors:
GUO YING (CN)
GAO HONG (CN)
Application Number:
PCT/CN2022/103803
Publication Date:
September 07, 2023
Filing Date:
July 05, 2022
Export Citation:
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Assignee:
SHENZHEN EXONEUGLIA BIOMEDICAL TECH CO LTD (CN)
International Classes:
C12N5/079; A61K35/30; A61P9/10; A61P25/00; A61P25/16; A61P25/28
Foreign References:
CN114262686A2022-04-01
CN106456672A2017-02-22
CN113564122A2021-10-29
US20170342380A12017-11-30
US20170095512A12017-04-06
Other References:
GOMEZ OSCAR, SANCHEZ-RODRIGUEZ MARIA A., ORTEGA-GUTIERREZ SILVIA, VAZQUEZ-VILLA HENAR, GUAZA CARMEN, MOLINA-HOLGADO FRANCISCO, MOL: "A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways", JOURNAL OF NEUROIMMUNE PHARMACOLOGY, SPRINGER US, BOSTON, vol. 10, no. 2, 1 June 2015 (2015-06-01), Boston , pages 309 - 317, XP093088967, ISSN: 1557-1890, DOI: 10.1007/s11481-015-9609-x
SANCHEZ-RODRIGUEZ MARIA A., GOMEZ OSCAR, ESTEBAN PEDRO F., GARCIA-OVEJERO DANIEL, MOLINA-HOLGADO EDUARDO: "The endocannabinoid 2-arachidonoylglycerol regulates oligodendrocyte progenitor cell migration", BIOCHEMICAL PHARMACOLOGY, ELSEVIER, US, vol. 157, 1 November 2018 (2018-11-01), US , pages 180 - 188, XP093088968, ISSN: 0006-2952, DOI: 10.1016/j.bcp.2018.09.006
TOMAS‐ROIG JORDI, WIRTHS OLIVER, SALINAS‐RIESTER GABRIELA, HAVEMANN‐REINECKE URSULA: "The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone‐Induced Central Nervous System Demyelination", CNS NEUROSCIENCE & THERAPEUTICS, WILEY-BLACKWELL PUBLISHING LTD., GB, vol. 22, no. 5, 1 May 2016 (2016-05-01), GB , pages 387 - 395, XP093088970, ISSN: 1755-5930, DOI: 10.1111/cns.12506
O GOMEZ; A SANCHEZ‐RODRIGUEZ; MQU LE; C SANCHEZ‐CARO; F MOLINA‐HOLGADO; E MOLINA‐HOLGADO: "Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways", BRITISH JOURNAL OF PHARMACOLOGY, WILEY-BLACKWELL, UK, vol. 163, no. 7, 12 July 2011 (2011-07-12), UK , pages 1520 - 1532, XP071102675, ISSN: 0007-1188, DOI: 10.1111/j.1476-5381.2011.01414.x
DOUVARAS, P.V. FOSSATI: "Generation and isolation of oligodendrocyte progenitor cells from human pluripotent stem cells", NATURE PROTOCOLS, vol. 10, no. 8, 2015, pages 1143 - 1154, XP055747582, DOI: 10.1038/nprot.2015.075
NAMCHAIW, P. ET AL.: "Temporal and partial inhibition of GLI1 in neural stem cells (NSCs) results in the early maturation of NSC derived oligodendrocytes in vitro", STEM CELL RES THER, vol. 10, no. 1, 2019, pages 272
Attorney, Agent or Firm:
JEEKAI & PARTNERS (CN)
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