Magnetically guided neurite outgrowth modulated by PIEZO1 in hiPSC-derived retinal ganglion cells

  • Mater Today Bio. 2025 Oct 21:35:102446. doi: 10.1016/j.mtbio.2025.102446.
I-Ting Chen  1  2 ,  Pei-Hsin Chu  2  3 ,  Shang-Hsiu Hu  4 ,  Shih-Kuo Chen  5  6 ,  Chuan-Chin Chiao  1 ,  Tien-Chun Yang  2  7
Affiliations
  • 1. Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan.
  • 2. Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
  • 3. Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei, 11031, Taiwan.
  • 4. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300044, Taiwan.
  • 5. Department of Life Science, National Taiwan University, Taipei, 106319, Taiwan.
  • 6. Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, 106319, Taiwan.
  • 7. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
PMID: 41209706 DOI: 10.1016/j.mtbio.2025.102446
Abstract

Retinal ganglion cell (RGC) axon degeneration is one of the major causes of vision loss in glaucoma, where regeneration remains limited by the central nervous system's low intrinsic repair capacity. We applied a magnetic-guided nanotechnology approach to modulate axon growth in human-induced pluripotent stem cell-derived RGCs (hiPSC-RGCs). Magnetic Neural Axon Vectors (MagNAVs)-multi granular Fe3O4 nanoparticles functionalized with rhodamine-were efficiently internalized and directed by an external magnetic field (MF), enhancing neurite elongation and alignment. The mechanosensitive ion channel PIEZO1 was expressed in both soma and neurites. Specifically, PIEZO1 inhibition by Dooku1 enhanced neurite elongation, and activation by Yoda1 elevated somatic calcium transients without affecting neurite outgrowth. Furthermore, two-photon calcium imaging revealed that somatic calcium activity was PIEZO1-dependent, whereas neuritic calcium signaling was more responsive to magnetic force. These results indicate that PIEZO1-mediated calcium influx may negatively regulate force-induced neurite elongation. This work demonstrates a nanomaterial-based strategy for targeted axon regeneration and highlights the mechanoregulatory role of PIEZO1.

Keywords
Axonal regeneration; Magnetic nanoparticles; PIEZO1; Retinal ganglion cells; hiPSC.
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