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조회 1630  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Multiscale, Hierarchically Patterned Topography for Directing Human Neural Stem Cells into Functional Neurons

Kisuk Yang, Hyunjung Jung, Hak-Rae Lee §, Jong Seung Lee, Su Ran Kim, Ki Yeong Song, Eunji Cheong, Joona Bang ‡*, Sung Gap Im §*, and Seung-Woo Cho †*

Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea
Department of Chemical and Biological Engineering, Korea University, Seoul 136-713, Republic of Korea
§ Department of Chemical and Biomolecular Engineering and KI for Nanocentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea

*Correspondence to Joona Bang, Sung Gap Im, Seung-Woo Cho

Abstract
Various biophysical and biochemical factors are important for determining the fate of neural stem cells (NSCs). Among biophysical signals, topographical stimulation by micro/nanopatterns has been applied to control NSC differentiation. In this study, we developed a hierarchically patterned substrate (HPS) platform that can synergistically enhance the differentiation of human NSCs (hNSCs) by simultaneously providing microscale and nanoscale spatial controls to facilitate the alignment of the cytoskeleton and the formation of focal adhesions. The multiscale HPS was fabricated by combining microgroove patterns (groove size: 1.5 μm), prepared by a conventional photolithographic process, and nanopore patterns (pore diameter: 10 nm), prepared from cylinder-forming block copolymer thin films. The hNSCs grown on the HPS exhibited not only a highly aligned, elongated morphology, but also a greatly enhanced differentiation into neuronal and astrocyte lineages, compared to hNSCs on a flat substrate (FS) or single-type patterned substrates [microgroove patterned substrate (MPS) and nanopore patterned substrate (NPS)]. Interestingly, the application of the HPS directed hNSC differentiation toward neurons rather than astrocytes. The expression of focal adhesion proteins in hNSCs was also significantly increased on the HPS compared to the FS, MPS, and NPS, likely a result of the presence of more focal contact points provided by nanopore structures. Inhibition of both β1 integrin-mediated binding and the intracellular Rho-associated protein kinase pathway of hNSCs eliminated the beneficial effects of the HPS on focal adhesion formation and actin filament alignment, which subsequently reduced hNSC differentiation. More importantly, hNSCs on the HPS differentiated into functional neurons exhibiting sodium currents and action potentials. The multiscale, hierarchically patterned topography would be useful for the design of functional biomaterial scaffolds to potentiate NSC therapeutic efficacy.

Keywords: hierarchically patterned substrate; topographical stimulation; human neural stem cell; focal adhesion; cytoskeleton alignment; differentiation

논문정보
- 형식: Research article
- 게재일: 2014년 07월 (BRIC 등록일 2014-08-06)
- 연구진: 국내연구진태극기
- 분야: Pharmacology
Dot/Icm 제 4 유형 커플링 단백질 복합체의 선택적 이펙터 단백질 인식[Nat. Commun.]
김현민
발표: 김현민 (KAIST)
일자: 2020년 9월 29일 (화) 오후 02시 (한국시간)
언어: 한국어
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