박희환 (아주대학교 의과대학, 현 Imperial College London) | 한빛사논문 > 한빛사

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아주대학교 의과대학, 현 Imperial College London

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Adv. Sci., Nov 03 2025, | https://doi.org/10.1002/advs.202507160 Mechanical Environment Afforded by Engineered Hydrogel Critically Regulates Survival of Neural Stem Cells Transplanted in the Injured Spinal Cord via Piezo1-Mediated Mechanotransduction

Hee Hwan Park^{1 2 †}, Yurim Kim^{3 4 †}, Byeong Seong Jang ^{1 2}, Simay Genişcan^{1 2}, Dong Hoon Hwang^{1 5}, Yeojin Seo ^{1 2}, Seung-Ah Jee ^{1 2}, Hyo Gyeong Seo ^{1 2}, Hyung Soon Kim ¹, Ariandokht Einisadr ^{1 2}, Ho-Jeong Kim ^{6 7}, Seolhee Lee ^{6 7}, Sangwoo Kwon⁸, Kyung Sook Kim⁸, Kang In Lee ⁹, Jae Young Lee ^{9 10}, Joo Min Park ^{4 6 7}, Young-Min Kim ^{3 4 *}, Soo-Chang Song ^{3 4 *}, Byung Gon Kim^{1 2 11 *}

¹Department of Brain Science, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
²Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea.
³Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
⁴University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.
⁵Wonju Medical Industry Technovalley, Wonju, 26354, Republic of Korea.
⁶Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126, Republic of Korea.
⁷Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
⁸Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul, 130-710, 02447, Republic of Korea.
⁹ToolGen Inc., Seoul, 07789, Republic of Korea.
¹⁰Department of Anatomy, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
¹¹Department of Neurology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.

^†These two authors H.H.P. and Y.K. equally contributed to this work.
^*Corresponding authors: correspondence to Young-Min Kim, Soo-Chang Song or Byung Gon Kim

Abstract

Neural stem cell (NSC) transplantation is a promising therapeutic approach for spinal cord repair, but poor graft survival remains a critical challenge. This work reports that the mechanical properties of the transplantation environment play a crucial role in NSC survival in the injured spinal cord. While this previously developed engineered hydrogel effectively creates extracellular matrix preventing cystic cavity formation, NSCs transplanted as a complex with 10% hydrogel exhibits poor survival. Remarkably, increasing the hydrogel concentration to 16%, creating a fivefold stiffer matrix, significantly enhances NSC graft survival. Using in vitro models with controlled substrate stiffness, this work finds that NSCs on stiffer substrates display enhanced adhesion, complex morphology, and increased viability. Electrophysiological recordings in NSCs reveal pressure-induced inward currents that are significantly reduced by Piezo1 inhibition. Pharmacological or siRNA inhibition of Piezo1 alters NSC morphology and reduces adhesion specifically on stiffer substrates. Importantly, CRISPR/Cas9-mediated Piezo1 gene editing significantly reduces graft survival in vivo when transplanted with 16% hydrogel, confirming that Piezo1-mediated mechanotransduction is essential for stiffness-dependent NSC survival. These findings reveal a previously unrecognized mechanism governing graft survival and suggest that optimizing mechanical properties of biomaterial scaffolds or directly targeting Piezo1-dependent mechanotransduction could substantially improve outcomes of cell-based therapies for neurological disorders.

논문정보

형식Research article
게재일2025년 11월 (BRIC 등록일 2025-11-04)
연구진국내 연구진
분야 바이오·의료융합 > 뇌인지과학

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