마우스 배아 줄기세포와 단백질 유래 만능 줄기세포의 도파민 뉴런으로의 분화능 비교

Abstract

During the progression of Parkinsons disease, stem cells can act as therapeutic agents to recover, or regenerate injured nervous system. In this study, two types of stem cells; mouse embryonic stem cells (mESCs) and protein-derived iPS cells (P-iPSCs), generated by non-viral methods, were differentiated into midbrain dopaminergic (mDA) neurons and compared its efficiency. In the undifferentiated stage, P-iPSCs expressed pluripotency markers without any difference to that of mES cells elucidating the fact that protein-based reprogramming was successful and stable as authentic ES cells. All two types of cells reached terminal matured mDA neurons while P-iPSCs showed more mDA neuron positive markers in protein levels as well as in mRNA levels when compared with mES cells. To investigate the mechanism of significantly advanced induction of mDA neurons in P-iPSCs, we analyzed histone modifications by genome-wide ChIP sequencing analysis and their corresponding microarray results. We found Wnt signaling was up-regulated while SFRP1, known as its counter-actor was suppressed more in P-iPSCs than mESCs. Moreover, dramatic change of expression level of epigenetic regulator, SIRT1 may be associated with differentiation efficiency. In 6-OHDA-induced Parkinsons rat model, both types of transplanted neural precursor cells showed rescued motor activity and migration in damaged striatum. Our results demonstrate that P-iPSCs can be an ultimate source for patient-specific cell therapy and efficient to replace damaged neurons in vivo as well.