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Direct Conversion of Human Umbilical Cord Blood into Induced Neural Stem Cells with SOX2 and HMGA2
International Journal of Stem Cells
Published online August 31, 2017;  
© 2017 Korean Society for Stem Cell Research.

Jae-Jun Kim1,2,*, Ji-Hee Shin1,2,*, Kyung-Rok Yu1,2,3,*, Byung-Chul Lee1,2, Insung Kang1,2, Jin Young Lee1,2, Da-Hyun Kim1,2, Yoojin Seo4,5, Hyung-Sik Kim4,5, Soon Won Choi1,2, Kyung-Sun Kang1,2

1Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea
2The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Korea
3Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, USA
4School of Medicine, Pusan National University, Busan, Korea
5Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
Correspondence to: Kyung-Sun Kang
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
Tel: +82-2-880-1246, Fax: +82-2-876-7610 E-mail: kangpub@snu.ac.kr
*These authors contributed equally to this work.
; Accepted July 29, 2017.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Recent advances have shown the direct reprogramming of mouse and human fibroblasts into induced neural stem cells (iNSCs) without passing through an intermediate pluripotent state. Thus, direct reprogramming strategy possibly provides a safe and homogeneous cellular platform. However, the applications of iNSCs for regenerative medicine are limited by the restricted availability of cell sources. Human umbilical cord blood (hUCB) cells hold great potential in that immunotyped hUCB units can be immediately obtained from public banks. Moreover, hUCB samples do not require invasive procedures during collection or an extensive culture period prior to reprogramming. We recently reported that somatic cells can be directly converted into iNSCs with high efficiency and a short turnaround time. Here, we describe the detailed method for the generation of iNSCs derived from hUCB (hUCB iNSCs) using the lineage-specific transcription factors SOX2 and HMGA2. The protocol for deriving iNSC-like colonies takes 1~2 weeks and establishment of homogenous hUCB iNSCs takes additional 2 weeks. Established hUCB iNSCs are clonally expandable and multipotent producing neurons and glia. Our study provides an accessible method for generating hUCB iNSCs, contributing development of in vitro neuropathological model systems.
Keywords : Human umbilical cord blood, Induced neural stem cells, Reprogramming, Direct conversion


May 2017, 10 (1)