FOS CDK1 Use for treating dysuric diseases using functionally improved stem cells by activating FOS or CDK1 gene

• Main Authors: SHIN DONG MYUNG, YU HWAN YEUL, LEE SEUNG UN
• Format: Patent
• Language: English; Korean
• Published: 18.11.2022
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TESTING; VINEGAR; WINE

The present invention relates to a therapeutic use for dysuric diseases using functionally improved stem cells by the activation of FOS or CDK1 genes, and specifically, the inventors conducted two-photon in vivo image analysis and single cell transcriptomic analysis and analyzed in vivo behavior of multipotent-MSCs (M-MSCs) derived from and engrafted human embryonic-SCs (hESCs) in IC/BPS animal models. Through longitudinal tow-photon image analysis, an interaction of MSC-bladder blood relationships engrafted as time goes by in a same living animal is visualized, indicating the gradual localization around blood vessels. A result of analyzing single cell transcriptomic analysis of engrafted M-MSCs indicated an expression change in various paths related to pericyte, cell adherence and cell stress. In particular, FOS and CDK1 play an important role in controlling movement/engraftment of M-MSCs and anti-inflammatory functions which determine an in-vivo treating capability of M-MSCs. Accordingly, the present invention provides accurate characteristics of transplanted MSCs to improve the understanding of a treatment mechanism of MSC treatment and enhance effects thereof and safety. 본 발명은 FOS 또는 CDK1 유전자 활성화를 통해 기능 향상된 줄기세포를 이용한 배뇨 장애 질환 치료 용도에 관한 것으로, 구체적으로, 본 발명자들은 이광자 생체 내 이미지 분석 및 단일세포 전사체 분석을 실시하여, IC/BPS 동물 모델에서 인간 배아-SCs(human embryonic-SCs; hESCs) 유래 생착된 다능성-MSCs(multipotent-MSCs; M-MSCs)의 생체 내(in vivo) 행동을 분석하였다. 종적 이광자 이미지 분석을 통해, 살아있는 동일한 생물에서 시간 경과에 따른 생착된 MSC-방광 혈관계의 상호작용을 가시화하였는데, 점진적인 혈관주위 국소화를 나타냈다. 생착된 M-MSCs의 단일세포 전사체 분석 결과, 혈관주위세포, 세포-부착 및 세포 스트레스와 관련된 여러 경로에서 발현 변화를 나타냈다. 특히, FOS 및 CDK1는 M-MSCs의 생체 내(in vivo) 치료 능력을 결정하는, M-MSCs의 이동/생착 및 항염증 기능을 조절하는데 중요한 역할을 수행한다. 종합하면, 본 발명은 이식된 MSCs의 정확한 특성을 제공하여, MSC 치료의 치료 기작에 대한 이해를 향상시키고, 이의 효과 및 안전성을 개선시킬 수 있다.