作者
Hyunah Lee, Hye Yeong Lee, Byeong Eun Lee, Daniela Gerovska, Soo Yong Park, Holm Zaehres, Marcos J Araúzo-Bravo, Jae-Ick Kim, Yoon Ha, Hans R Schöler, Jeong Beom Kim
发表日期
2020/6/23
期刊
Elife
卷号
9
页码范围
e52069
出版商
eLife Sciences Publications, Ltd
简介
Generation of autologous human motor neurons holds great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows generation of target cells from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic that are not scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing POU5F1(OCT4) and LHX3. Our strategy enables scalable production of pure iMNs because of the transient acquisition of proliferative iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited hallmarks of spinal motor neurons including transcriptional profiles, electrophysiological property, synaptic activity, and neuromuscular junction formation. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in rodent SCI model. Together, our advanced strategy will provide tools to acquire sufficient human iMNs that may represent a promising cell source for personalized cell therapy.
引用总数