Sequentially induced motor neurons from human fibroblasts facilitate locomotor recovery in a rodent spinal cord injury model
Cited 0 times inCited 0 times in
- Sequentially induced motor neurons from human fibroblasts facilitate locomotor recovery in a rodent spinal cord injury model
- Lee, Hyunah; Lee, Hye Yeong; Lee, Byeong Eun; Gerovska, Daniela; Park, Soo Yong; Zaehres, Holm; Araúzo-Bravo, Marcos J; Kim, Jae-Ick; Ha, Yoon; Schöler, Hans R; Kim, Jeong Beom
- Issue Date
- ELIFE SCIENCES PUBLICATIONS LTD
- ELIFE, v.9, pp.e52069
- 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.
- Appears in Collections:
- BIO_Journal Papers
- Files in This Item:
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.