초록 ▼

○ ALS 치료위한 인간지방줄기세포 유래 세포유전자 치료제 개발 2종 (ADSC+IGF1, ADSC+BDNF)○ ADSC+IGF1과 ADSC+BDNF 이식 세포군 운동신경세포로 분화, 행동학적 치료효과 및 세포사멸 억제효과 검증
○ ALS 치료위한 인간신경줄기세포 유래 세포유전자 치료제 개발 1종 (F3.OL2.Shh)
○ ADSC+IGF1과 ADSC+BDNF 이식 세포군보다 신경세포 분화한 이식군의 치료효과 향상 검증
○ 세포유전자 치료제 분화위한 조건 확립 (인간 지방줄기세포, 인간 신경줄기세포)
○ 이식방

○ ALS 치료위한 인간지방줄기세포 유래 세포유전자 치료제 개발 2종 (ADSC+IGF1, ADSC+BDNF)○ ADSC+IGF1과 ADSC+BDNF 이식 세포군 운동신경세포로 분화, 행동학적 치료효과 및 세포사멸 억제효과 검증
○ ALS 치료위한 인간신경줄기세포 유래 세포유전자 치료제 개발 1종 (F3.OL2.Shh)
○ ADSC+IGF1과 ADSC+BDNF 이식 세포군보다 신경세포 분화한 이식군의 치료효과 향상 검증
○ 세포유전자 치료제 분화위한 조건 확립 (인간 지방줄기세포, 인간 신경줄기세포)
○ 이식방법 비교 및 확정 (intracerebroventricular 방법)
○ ALS 질환에 연관성있는 인간 성상세포 분비 물질 분석
○ ALS 동물 모델에서 세포치료제 이식 후 global 유전자 발현 변화 분석

Abstract ▼

Ⅰ. Objectives
Neurotrophic factors were transfected into ALS-derived ADSCs after neural differentiation. The aims of this study is that these therapeutic cells were transplanted into ALS animal model to improve functional recovery and extend their life span.

Ⅱ. Materials and methods
○ E

Ⅰ. Objectives
Neurotrophic factors were transfected into ALS-derived ADSCs after neural differentiation. The aims of this study is that these therapeutic cells were transplanted into ALS animal model to improve functional recovery and extend their life span.

Ⅱ. Materials and methods
○ Establishment of human adipose-derived stem cells and neural stem cells
○ Establishment of ADSC+IGF-I and ADSC+BDNF
○ Establishment of Olig2-overexpressed human neural stem cells
○ Characterization of transplanted stem cells
- Analysis of cellular characters (RT-PCR, Immunocytocgemistry, Electrophysiology)
○ Differentiation of human stem cells into motor neurons
- Culture in medium with bFGF and SHH
○ Transplantation of stem cells into SODG93A animal models
- 4x105 cells by ICV and IV
○ Test of behavior and life span
(1) Rota-rod performance
(2) Paw grip endurance
(3) Hindlimb-extension reflex
(4) End-stage life-span
○ Analysis of MRI image to trace the transplanted stem cells
○ Analysis of differentiation of transplanted cells and microenvironment
○ microarray analysis
○ Pure culture of human astrocytes
○ Analysis of cytokine/chemokine of human astrocytes

Ⅲ. Results
○ Establishment of cell-based gene therapy from human ADSC for ALS (ADSC+IGF1, ADSC+BDNF)
○ Confirmation of the neuronal differentiation, behavior test and cell death of ADSC+IGF1 and ADSC+BDNF
○ Establishment of cell-based gene therapy from human NSCs for ALS (F3+OL2.Shh)
○ Improvement of therapeutic effects of neuronal differentiated ADSC+IGF1 and ADSC+BDNF than undifferentiated one.
○ Establishment of differentiation methods for ADSCs and NSCs
○ Establishment of transplantation methods (intracerebroventricular injection)
○ Analysis of cytokine/chemokine secreted from astrocytes
○ Global gene profiling for stem cell-transplanted ALS animal model

Ⅳ. Future plans of this study
○ The expectation of protection, functional recovery, extended life span of motor neurons after the transplantation of neurotrophic factor overexpressed human ADSC.
○ Cell-based gene therapy may be given therapeutic effects for ALS patients.
○ Neurotrophic factor from transplanted stem cells will be expected to improve angiogenesis and tissue recovery in impaired spinal cord.
○ These cell-based gene therapy will be expected to be a useful tool for ALS.