초록 ▼

생체 내 미세환경 조절과 줄기세포를 이용하여 허혈성 뇌손상 치료의 핵심 기술을 개발을 위하여
o 골수 조직재생 세포원 (MSC, EPC)의 가동화 기술을 이용한 급성 뇌졸증 치료 기술.
o 신경계 특이적 분화유도를 통한 기능성 중간엽줄기세포 치료제의 개발 및 실용화를 위한 유효성/안전성 평가.
o 허혈성 뇌손상 부위에서의 미세환경을 유전자/단백질/줄기세포를 이용하여 조절하여 내인성 신경줄기세포와 이식한 줄기세포의 생착능 및 치유능을 향상.
o 뇌졸중 모델에서 생체 내 신경재생을 유도하고, 미세환경 조절과

생체 내 미세환경 조절과 줄기세포를 이용하여 허혈성 뇌손상 치료의 핵심 기술을 개발을 위하여
o 골수 조직재생 세포원 (MSC, EPC)의 가동화 기술을 이용한 급성 뇌졸증 치료 기술.
o 신경계 특이적 분화유도를 통한 기능성 중간엽줄기세포 치료제의 개발 및 실용화를 위한 유효성/안전성 평가.
o 허혈성 뇌손상 부위에서의 미세환경을 유전자/단백질/줄기세포를 이용하여 조절하여 내인성 신경줄기세포와 이식한 줄기세포의 생착능 및 치유능을 향상.
o 뇌졸중 모델에서 생체 내 신경재생을 유도하고, 미세환경 조절과 관련된 치료기전을 규명하여, 전 임상기반을 구축.
o 줄기세포치료제의 생착능 향상을 위한 세포이식용 기능성 생체소재와 성장인자 전달시스템을 개발
o 뇌졸중 유발 시 대뇌 미세환경 내에 존재하는 Shh 반응세포들의 증식, 분화 및 이동 과정을 규명 및 조절기술을 개발함.
(출처:요약서 3p)

Abstract ▼

This proposal aims to develop core technologies for treatment of ischemic brain injury by using stem cells and by controlling tissue microenvironment. More specific aims are followed.
1) technology development for acute ischemic tissue injury by using MSC/EPC mobilization
2) development of fun

This proposal aims to develop core technologies for treatment of ischemic brain injury by using stem cells and by controlling tissue microenvironment. More specific aims are followed.
1) technology development for acute ischemic tissue injury by using MSC/EPC mobilization
2) development of functional MSC by neura- specific differentiation and their efficacy and safety for clinical application.
3) improvement in cell survival and engraftment of transplanted cells and stimulation of endogenous NSC by controlling tissue microenvironment.
4) preclinical assessment of therapeutic cells and microenvironment-modulating factors for acute ischemic brain injury.
5) development of cell and growth factor delivery system for improved cell engraftment.
6) identification of Shh-responsible cells in ischemic brain injury and elucidation of mechanism of their proliferation, differentiation, and migration.

We developed core technologies for stem cell-based therapies and microenvironment control for the treatment of ischemic brain injury.
1) 1st subproject:
- Identification of SP's EPC mobilizer function and comparative study with G-CSF
- Identification of SP-responsible stem cell pools in bone marrow
- Establishment of acute ischemic stroke model and technologies of better engraftment
- Analysis of MSC/EPC mobilization time kinetic
- Evaluation of homing and SP's tissue protective effect in ischemic stroke model
- Analysis of microenvironmental changes in BM after SP-induced MSC/EPC mobilization
- Analysis of MSC/EPC mobilizing capacity and stem cell pools as endogeneous reparative stem cells at different ages and individuals
- Safety test and toxicological test of SP and MSC, EPC
2) 2nd subproject:
- chromatin structures before & after neural differentiation
- Screening of reprogramming sensitizer of MSC
- Investigation of non-genetic factors for neural differentiation of MSC
- Efficacy evaluation of candidate factors
- Improvement of cell transplantation technologies in acute ischemic brain injury
- Improvement of cell engraftment in chronic stroke model
- Safety test of function-improved cell therapeutics
3) 3rd subproject:
- Molecular control of ischemic brain microenvironment
- Regulation of ischemic brain microenvironment by adipose derived stem cells
- Regulation of ischemic brain microenvironment by blood born CD34+ cells
- Improvement of cell delivery technologies by microenvironmental control and their efficacy evaluation in acute and chronic ischemic brain injury
4) 4th subproject
- Establishment of stroke and rehabilitation animal model
- Efficacy test of erythropoietin, G-CSF, and Substance-P
- Standardization of neural regeneration effect
- Improvement of cell therapeutic efficiency
- Development of clinical study protocol and investigative clinical study
5) 5th subproject
- Cell transplantation technologies for improved cell proliferation, differentiationl and engraftment
- Delivery system of genes and factors for better intake rate of transplanted cells
- Combination therapies for stem cell, growth factors, biomaterials, genes for ischemic brain injury
6) 6th subproject
- Analysis of Shh signaling activity and Shh responsive cells in ischemic brain injury
- Elucidation of the role of Shh responsive cells in tissue regeneration after the stroke
- Effects of regulation of Shh signaling pathway on cell proliferation, differentiation, migration
- Investigation of possible positive effect of Shh signaling on tissue repair
- Investigation of chromatin status and gene expression profiles in Shh-responsive NSC

Based on our research products, ideal stem cell therapeutic stimulating natural healing mechanism will be developed. Additionally, The interrelationship between stem cell pool and microenvironmental control will be identified and core technologies will be developed. Finally, successful new drug to intervene acute ischemic stroke, spinal cord injury, acute myocardial infarction will be developed and royalty from patents will be obtained and medical imports will be decreased
(출처:SUMMARY 6~7p)

목차 Contents

• 표지 ... 1제 출 문 ... 2보고서 요약서 ... 3요 약 문 ... 4SUMMARY ... 6CONTENTS ... 8목차 ... 9제1장 연구개발과제의 개요 ... 10 제1절 연구개발의 목적 ... 10 제2절 연구개발의 필요성 ... 11제2장 국내외 기술개발 현황 ... 16 제1절 연구개발 대상 기술의 국내·외 현황 ... 16제3장 연구개발수행 내용 및 범위 ... 28 제1절 제 1세부 ... 28 제2절 제 2세부 ... 30 제3절 제 3세부 ... 31 제4절 제 4세부 ... 32 제5절 제 5세부 ... 33 제6절 제 6세부 ... 34제4장 연구개발 결과 ... 36 제1절 제 1세부 ... 36 제2절 제 2세부 ... 42 제3절 제 3세부 ... 44 제4절 제 4세부 ... 50 제5절 제 5세부 ... 56 제6절 제 6세부 ... 62제4장 목표달성도 및 관련분야에의 기여도 ... 68 제1절 계획대비 달성도 (선정 시 제시된 연구목표) ... 68제5장 연구개발결과의 활용계획 ... 81제6장 연구개발과정에서 수집한 해외과학기술정보 ... 83제7장 연구시설·장비 현황 ... 86제8장 참고문헌 ... 87끝페이지 ... 95