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Kafe 바로가기주관연구기관 | 한국생명공학연구원 Korea Research Institute of Bioscience and Biotechnology |
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연구책임자 | 이상철 |
참여연구자 | 김세윤 , 김재호 |
보고서유형 | 최종보고서 |
발행국가 | 대한민국 |
언어 | 한국어 |
발행년월 | 2017-11 |
과제시작연도 | 2016 |
주관부처 | 과학기술정보통신부 Ministry of Science and ICT |
등록번호 | TRKO201800002969 |
과제고유번호 | 1711042812 |
사업명 | 바이오.의료기술개발 |
DB 구축일자 | 2018-04-14 |
키워드 | 전분화능 줄기세포.역분화 줄기세포.독성.약효.신약개발.pluripotent stem cell.iPSCs.Toxicity.efficacy.Drug development. |
인간 줄기세포 기반 신경, 간, 심근세포 분화 원천기술 개발 및 각각의 세포에 대한 독성, 약효 평가 시스템 구축과 기술을 개발하기 위해 아래와 같은 연구를 수행함.
첫째, 인간 줄기세포 유래 신경, 간, 심근, 뇌혈과내피 및 성상세포로의 분화 시스템과 QA/QC 시스템을 확립함.
둘째, 각세포의 특성을 분석하고 생물학적 기능성을 확인했으며, 분자적, 유전자적 분석을 진행함.
셋째, 독성 및 약효 시험을 위한 세포의 양적 확보를 위한 배양 기술을 획득했으며, 기존에 사용되고 있는 독성 시험과 비
인간 줄기세포 기반 신경, 간, 심근세포 분화 원천기술 개발 및 각각의 세포에 대한 독성, 약효 평가 시스템 구축과 기술을 개발하기 위해 아래와 같은 연구를 수행함.
첫째, 인간 줄기세포 유래 신경, 간, 심근, 뇌혈과내피 및 성상세포로의 분화 시스템과 QA/QC 시스템을 확립함.
둘째, 각세포의 특성을 분석하고 생물학적 기능성을 확인했으며, 분자적, 유전자적 분석을 진행함.
셋째, 독성 및 약효 시험을 위한 세포의 양적 확보를 위한 배양 기술을 획득했으며, 기존에 사용되고 있는 독성 시험과 비교 분석을 진행함.
넷째, 질환표현형 역분화 줄기세포를 확보했으며, 다양한 질환 관련 신약 개발 시스템을 구축했음.
다섯째, 기존의 약물에 대한 독성 및 약효에 관한 데이터베이스를 구축하고, 연구자 및 일반인이 접근 및 이용 가능하도록 홈페이지를 구축했음.
여섯째, 간세포 독성/약효 평가 시스템의 산업적 적용을 위한 HTS(high Throughput Screening) 플랫폼에 기반한 간세포 배양기술과 독성평가 제반 시스템을 연구 개발했음
위의 내용을 바탕으로, 현재 이용되고 있는 독성 및 약효 평가 시스템을 극복하는 인간줄기세포 기반 신약 독성 및 약효 평가 시스템 구축을 기술을 확보했음
( 출처 : 보고서 요약서 3p )
Purpose & Contents
Based on normal and disease-specific stem cells, 1) establishing standardization/optimization of cellular differentiation to produce cells for toxicity/efficacy test system, 2) establishing QA/QC system to apply them to toxicity/efficacy evaluation system and verifying these sy
Purpose & Contents
Based on normal and disease-specific stem cells, 1) establishing standardization/optimization of cellular differentiation to produce cells for toxicity/efficacy test system, 2) establishing QA/QC system to apply them to toxicity/efficacy evaluation system and verifying these system, taken together, 3) developing technologies for stem cell-derived toxicity/efficacy evaluation system
The first period: Establishment of toxicity/efficacy evaluation system based on stem cell
1st year: Optimization of stem cell differentiation technology
- Optimization of stem cell differentiation technology
- Evaluation of differential specification of disease-specific stem cell
- Evaluation of tissue-specific differentiated cells
- Establishment of chemical DB for toxicity/efficacy evaluation system
2nd year: Validation of differentiated cells to apply for toxicity/efficacy evaluation system
- Systematization of toxicity/efficacy evaluation system based on differentiated cells.
- Evaluation of differentiated cell’s reactivity for negative or positive chemicals of toxicity/efficacy test system.
- Foundation of stable and large scale culture system
- Validation of disease-model with differentiated cell from disease-specific stem cells.
3rd year: Establishment of toxicity/efficacy evaluation system applied for stem cell-derived differentiated cells
- Establishment of toxicity evaluation protocol and optimization of system
- Development and optimization of efficacy evaluation system
- Functional promotion through comparison and analysis with original evaluation system
- Optimization of disease-specific differentiated cells
The second period: Establishment of stem cell derived toxicity/efficacy evaluation system and security of a foundation for practical use
4th year: Optimization/standardization of toxicity/efficacy evaluation system with stem cell derived differentiated cells
- OA/QC of toxicity/efficacy evaluation system
- Standardization of toxicity/efficacy evaluation system
- Optimization of toxicity/efficacy evaluation protocol with disease-model cell
- Comparison with original toxicity/efficacy evaluation system
5th year: Establishment of foundation for practical use of stem cell derived toxicity/efficacy evaluation system
- Toxicity/efficacy evaluation of new and candidate compounds with disease-model cells
- Optimization of toxicity/efficacy evaluation system with disease-model cells
- Establishment of fundamental for practical use of toxicity/efficacy evaluation system
- Establishment of normal or disease-specific cell-distributing system
Results
■ Establishment of stem cell-based biomimicry brain microenvironment and development of neuronal toxicity and efficacy test system
♦ i. We optimized the condition of various subtype neuronal differentiation from human embryonic stem cells
♦ ii. We optimized the culture condition of neural precursor cells from human embryonic stem cells and secured the cells for drug toxicity/efficacy evaluation
♦ iii. We conducted gene expression patterns analysis in neural progenitor cells and mature neurons
♦ iv. We checked the drug toxicity with differentiated neurons and established the drug toxicity/efficacy test system
♦ v. We made induced pluripotent stem cells(iPSCs) from alzheimers disease patient’and parkinson’s disease patients’ somatic cells and secured differentiation system into various neurons related with neurodegenerative diseases.
♦ vi. We identified gene expression patterns in neurons differentiated from disease-derived iPSCs
♦ vii. We secured the differentiation condition of astrocyte from human embryonic stem cells for the construction of the brain microenvironment
■ Development of standard protocols and systems to culture human stem cell-derived hepatocytes and evaluate drug toxicity/efficacy
♦ Establishment of human embryonic stem cell-derived hepatocytes in culture:
- we aim to develop and optimize the best cell culture protocol for obtaining hepatocytes differentiated from human embryonic stem cells.
♦ Foundation of hepatocyte QA/QC system:
- we plan to set up the highly efficient QA/QC system which will be used to evaluate physiological properties of differentiated hepatocytes.
♦ Establishment of hepatocyte toxicity evaluation system:
- We aim to comprehensively test drug toxicity and toxic responses throughout general toxicology, metabolomics, toxicogenomics as well as immunotoxicity.
■ Development of standard protocol for myocardiac differentiation of stem cells and cell-based evaluation system for effectiveness and cardiotoxicity of drugs
♦ Establishment of optimal differentiation protocol of human pluripotent stem cells to cardiac muscle
♦ Measurement of ion channel activities of differentiated cardiac muscle
♦ Establishment of stem cell-derived cardiac muscle for measurement of drug toxicity and efficacy
♦ Development of drug efficacy measurement system for cardiac muscle
♦ Development of cardiac toxicity measurement system
♦ Development of drug efficacy and toxicity evaluation system based on measurement of ion channels
■ Development of cell-based in vitro disease model system for nonclinical drug screening and toxicology testing
♦ We have successfully generated 5 different disease-specific human induced pluripotent stem cells (DM1, GM1, Diabetes, Behcet's, and FD) from patient-derived human somatic cells and differentiated into disease target cells (neural cells, cardiac cells, immune cells, beta cells, and Osteolineage- specific cells).
♦ Disease-specific differentiated cells were systematically evaluated and qualified using 'Omics technology' and suggested as disease-specific model cells.
Expected Contribution
i. It will be able to establish new toxicity test data substituting the preclinical data
ii. It will be able to establish a variety of neurons & BMECs derived from various PSC sources
iii. It will be able to develop new drug candidates for treatment of neurological diseases
iv. It will be applicable to drug development for treatment of diseases related to blood-retinal barrier that is structurally similar to BBB
v. Based on our knowhow and technologies, we will continue to develop HTS-based hepatotoxicity/drug efficacy screening systems
vi. In addition to making significant contributions on the field of stem cell biology, we ultimately aim to utilize our database and technological advances in biotechnological areas such as drug development and toxicity screening via technology transfer.
vii. It will contribute to provide valuable resources of disease-specific and tissue-specific human cells and disease-specific drug screening system for their use in therapeutics/drug discovery.
( 출처 : SUMMARY 5p )
과제명(ProjectTitle) : | - |
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연구책임자(Manager) : | - |
과제기간(DetailSeriesProject) : | - |
총연구비 (DetailSeriesProject) : | - |
키워드(keyword) : | - |
과제수행기간(LeadAgency) : | - |
연구목표(Goal) : | - |
연구내용(Abstract) : | - |
기대효과(Effect) : | - |
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