김해원 (단국대학교 조직재생공학연구원/치과대학) | 한빛사논문 > 한빛사

한빛사논문

조회398

단국대학교 조직재생공학연구원/치과대학

CV File 346 kb

Adv. Sci., 10 July 2024 | https://doi.org/10.1002/advs.202400586 Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification

Yu-Meng Li ^{1 2}^†, Yunseong Ji ^{1 3}^†, Yu-Xuan Meng ^{1 2}^†, Yu-Jin Kim ⁴, Hwalim Lee ^{1 4}, Amal George Kurian ^{1 2}, Jeong-Hui Park ^{1 5}, Ji-Young Yoon ^{1 2}, Jonathan C Knowles ^{1 2 5 6}, Yunkyu Choi ⁷, Yoon-Sik Kim ^{1 8 9}, Bo-Eun Yoon ^{1 8 9}, Rajendra K Singh^{1 2}, Hae-Hyoung Lee^{1 2 4}, Hae-Won Kim ^{1 2 4 5 8 10 11 *}, Jung-Hwan Lee^{1 2 4 5 8 10 *}

¹Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

²Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

³Fuel Cell Laboratory, Korea Institute of Energy Research (KIER), Daejeon, 34129, Republic of Korea.

⁴Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

⁵UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

⁶Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF, UK.

⁷Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Republic of Korea.

⁸Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

⁹Department of Molecular Biology, Dankook University, Cheonan, 31116, Republic of Korea.

¹⁰Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea.

¹¹Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

^†Y.-M.L., Y.J., and Y.-X.M. contributed equally to this work as co-first authors.
^*Corresponding authors: correspondence to Hae-Won Kim or Jung-Hwan Lee

Abstract

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m⁻¹, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02–0.1 S m⁻¹) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m⁻¹). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-11)
연구진국내(교신)+국외 연구진
분야 의약학 > 재생의학

댓글 작성 로그인

CV 열람하기

연락처 보기