한빛사논문
Boram Son1,2†, Sora Park1†, Sungwoo Cho1, Jeong Ah Kim3, Seung-Ho Baek4, Ki Hyun Yoo5, Dongoh Han5, Jinmyoung Joo6, Hee Ho Park2,7*, and Tai Hyun Park1,8*
1School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
2Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
3Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju, Chungbuk 28119, Republic of Korea.
4Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), Ulsan 44429, Korea.
5SIMPLE Planet Inc., 48 Achasan-ro 17-gil, Seongdong-gu, Seoul 04799, Korea.
6Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
7Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea.
8Department of Nutritional Science and Food Management, Ewha Womans University, Seodaemun-gu, Seoul 03760, Republic of Korea.
*Address correspondence to: Hee Ho Park, Tai Hyun Park
†These authors contributed equally to this work.
Abstract
Background: To improve the efficiency of neural development from human embryonic stem cells, human embryoid body (hEB) generation is vital through 3-dimensional formation. However, conventional approaches still have limitations: long-term cultivation and laborious steps for lineage determination. Methods: In this study, we controlled the size of hEBs for ectodermal lineage specification using cell-penetrating magnetic nanoparticles (MNPs), which resulted in reduced time required for initial neural induction. The magnetized cells were applied to concentrated magnetic force for magnet-derived multicellular organization. The uniformly sized hEBs were differentiated in neural induction medium (NIM) and suspended condition. This neurally induced MNP-hEBs were compared with other groups. Results: As a result, the uniformly sized MNP-hEBs in NIM showed significantly improved neural inductivity through morphological analysis and expression of neural markers. Signaling pathways of the accelerated neural induction were detected via expression of representative proteins; Wnt signaling, dopaminergic neuronal pathway, intercellular communications, and mechanotransduction. Consequently, we could shorten the time necessary for early neurogenesis, thereby enhancing the neural induction efficiency. Conclusion: Overall, this study suggests not only the importance of size regulation of hEBs at initial differentiation stage but also the efficacy of MNP-based neural induction method and stimulations for enhanced neural tissue regeneration.
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