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1. (WO2018034519) METHOD FOR ENHANCING DIFFERENTIATION EFFICIENCY AND MATURATION LEVEL OF STEM CELL-DERIVED CARDIAC MUSCLE CELLS BY USING NECROX
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Pub. No.: WO/2018/034519 International Application No.: PCT/KR2017/008978
Publication Date: 22.02.2018 International Filing Date: 17.08.2017
IPC:
C12N 5/077 (2010.01) ,A61K 35/34 (2006.01)
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07
Animal cells or tissues
071
Vertebrate cells or tissues, e.g. human cells or tissues
077
Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
35
Medicinal preparations containing material or reaction products thereof with undetermined constitution
12
Materials from mammals or birds
34
Muscles; Heart
Applicants:
서울대학교병원 SEOUL NATIONAL UNIVERSITY HOSPITAL [KR/KR]; 서울시 종로구 대학로 101 (연건동) (Yeongeon-dong) 101, Daehak-ro, Jongno-gu, Seoul 03080, KR
Inventors:
김효수 KIM, Hyo-Soo; KR
양한모 YANG, Han-Mo; KR
김주영 KIM, Ju-Young; KR
이주은 LEE, Joo-Eun; KR
Agent:
이명진 LEE, Myoung-Jin; KR
Priority Data:
10-2016-010467918.08.2016KR
10-2017-010371216.08.2017KR
Title (EN) METHOD FOR ENHANCING DIFFERENTIATION EFFICIENCY AND MATURATION LEVEL OF STEM CELL-DERIVED CARDIAC MUSCLE CELLS BY USING NECROX
(FR) PROCÉDÉ D'AMÉLIORATION DE L'EFFICACITÉ DE DIFFÉRENCIATION ET DU NIVEAU DE MATURATION DE CELLULES DE MUSCLE CARDIAQUE DÉRIVÉES DE CELLULES SOUCHES À L'AIDE DE NÉCROX
(KO) NECROX를 이용한 줄기세포 유래 심근세포의 분화 효율 및 성숙도 증진 방법
Abstract:
(EN) The present inventors completed the present invention by performing formal research in order to promote differentiation efficiency of stem cell-derived cardiac muscle cells and enhance the maturation level of the same and, as a result, and confirming that, in a group treated with NecroX, the efficiency of differentiation into stem cell-derived cardiac muscle cells is increased and more mature cardiac muscle cells can be obtained in a short period of time. According to the present invention, the stem cell-derived cardiac muscle cells treated with NecroX have a larger and thicker cell size compared to those of control groups, are strong, and display a dense actin structure, thereby indicating that stem cell-derived cardiac muscle cells induced through NecroX treatment can be prepared into cardiac muscle cells with increased maturation level, and thus when NecroX is treated, the differentiation of stem cell-derived cardiac muscle cells can be induced with high efficiency and high purity. Therefore, it is expected that NecroX of the present invention is helpful as a useful material, which can also increase the differentiation efficiency and maturation level of other differentiated cells, for the preparation of a heart disease model by establishing cardiac muscle cell differentiation from patient-specific induced pluripotent stem cells.
(FR) Les présents inventeurs ont élaboré la présente invention en effectuant une recherche formelle afin de favoriser l'efficacité de différenciation de cellules de muscle cardiaque dérivées de cellules souches et d'améliorer le niveau de maturation de celles-ci et, en conséquence, et en confirmant que, dans un groupe traité avec NécroX, l'efficacité de la différenciation en cellules de muscle cardiaque dérivées de cellules souches est augmentée et des cellules de muscle cardiaque plus matures peuvent être obtenues en une courte période de temps. Selon la présente invention, les cellules de muscle cardiaque dérivées de cellules souches traitées avec NécroX ont une taille de cellule plus grande et plus épaisse par rapport à celles des groupes de contrôle, sont fortes, et affichent une structure d'actine dense, ce qui permet d'indiquer que des cellules de muscle cardiaque dérivées de cellules souches induites par un traitement avec NécroX peuvent être préparées pour former des cellules de muscle cardiaque ayant un niveau de maturation accru et, par conséquent, lorsque le NécroX est traité, la différenciation de cellules de muscle cardiaque dérivées de cellules souches peut être induite avec une efficacité élevée et une pureté élevée. Par conséquent, il est attendu que le NécroX selon la présente invention est efficace en tant que matériau utile, ce qui peut également augmenter l'efficacité de différenciation et le niveau de maturation d'autres cellules différenciées, pour la préparation d'un modèle de maladie cardiaque par l'établissement d'une différenciation de cellules de muscle cardiaque par rapport à des cellules souches pluripotentes induites spécifiques au patient.
(KO) 본 발명자들은 줄기세포 유래 심근세포의 분화 효율을 증진시키고 성숙도를 향상시키기 위해 예의 연구한 결과, 네크로엑스(NecroX) 처리군에서 줄기세포기반 심근세포로의 분화효율이 증가하였을 뿐만 아니라 더 성숙한 심근세포를 단기간에 획득할 수 있다는 사실을 확인하고, 본 발명을 완성하였다. 본 발명에 따른 NecroX의 처리로 줄기세포 유래 심근세포는 세포의 크기가 대조군에 비해 크고 굵으며, 튼튼할 뿐만 아니라 치밀한 액틴의 구조를 보여, NecroX 처리로 유도된 줄기세포유래 심근세포는 성숙도가 높아진 심근세포를 제작할 수 있음을 보여주는바, 따라서 NecroX를 처리하면 줄기세포에서 유래된 심근세포의 고효율, 고순도 분화를 유도할 수 있다. 이에, 본 발명의 NecroX는 다른 분화세포의 분화효율과 성숙도도 증가시킬 수 유용한 물질로서 환자 맞춤형 유도만능줄기세포에서 심근세포의 분화를 확립해 심장질환 모델을 제작하는데 도움이 될 것으로 기대된다.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: Korean (KO)
Filing Language: Korean (KO)