유전자 조작을 통한 신경전구세포 유래 중뇌도파민 신경세포의 성숙도 및 생존력 증가를 위한 연구

Abstract

Developmental information can be aided in stem cell biology to produce tissue-specific cells. Nurr1 and Foxa2 are potential candidates for midbrain-type dopamine (mDA) neuron generation for experimental and therapeutic uses in Parkinson’s disease (PD), as forced expression of these genes in neural stem/precursor cells(NPCs) yielded cells acquiring a completed battery of mDA neuron-specific genes. However, simple overexpression without considering their expression patterns in the developing midbrain frequently generated mDA cells without sufficient levels of maturation and long-term maintenance in vitro and in vivo after transplantation. We here show that the physiologic level and timing of Nurr1 and Foxa2 can be recapitulated in NPCs by choosing right vectors and promoters. The controlled expressions, combined with a strategy for the transgene expression maintenance, caused generation of fully mature mDA neurons equipped with presynaptic DA neuron functions, phenotypes of which were maintained for long-term cultures, and maturity and functionality of which were rather increased long after cultures.