中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (4): 1586-1594.doi: 10.4103/NRR.NRR-D-24-00455

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

通过靶向调控 PTEN 加强损伤脊髓中的神经干细胞整合

  

  • 出版日期:2026-04-15 发布日期:2025-07-28

Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation

Simay Genişcan1, 2, #, Hee Hwan Park1, 2, #, Hyung Soon Kim1, 2, #, Seokjin Yoo1 , Hyunmi Kim1, 3, Byeong Seong Jang1, 2, Dong Hoon Hwang1, †, Kevin K Park4 , Byung Gon Kim1, 2, 3, 5, *   

  1. 1 Ajou University School of Medicine, Department of Brain Science, Suwon, Republic of Korea;  2 Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea;  3 AI Superconvergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon, Republic of Korea;  4 Department of Opthalmology, Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA;  5 Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea  † Current address: Wonju Medical Industry Technovalley, Wonju, Republic of Korea
  • Online:2026-04-15 Published:2025-07-28
  • Contact: Byung Gon Kim, MD, PhD, kimbg@ajou.ac.kr.
  • Supported by:
    This study was supported by the National Research Foundation of Korea, Nos. 2021R1A2C2006110, 2021M3E5D9021364, 2019R1A5A2026045 (to BGK); the Korea Initiative for Fostering University of Research and Innovation (KIURI) Program of the NRF funded by the MSIT (to HK); No. NRF2021M3H1A104892211 (to HSK).

摘要:

脊髓损伤导致神经网络断裂,从而永久性丧失神经功能。移植神经干细胞(NSCs)有望修复中断的连接。然而,确保神经干细胞存活并融入宿主神经回路仍然是一项艰巨的挑战。在此,实验研究了改变神经干细胞的内在特性是否能增强其移植后的整合。重点是磷酸酶和天丝同源物(PTEN),它是一种特征明确的肿瘤抑制因子,已知能关键性地调节神经元存活和轴突再生。通过删除小鼠神经干细胞中的Pten,可观察到神经元的生长速度加快,对神经毒性环境的抵抗力增强。在移植到损伤脊髓后,Pten缺陷的神经干细胞表现出更高的存活率和更广泛的喙尾分布。为了研究部分抑制PTEN的潜在影响,用靶向PTEN的短发夹RNA(shRNA)处理大鼠神经干细胞,PTEN被敲除后,体外神经元的生长、存活和神经球的运动性都得到了显著改善。将经过 shPTEN 处理的神经干细胞移植到损伤的脊髓中,也会导致移植存活率和迁移率的提高,其程度与完全缺失的情况相似。此外,PTEN抑制促进了从病变中心迁移的神经干细胞来源神经元的神经元伸长。这些研究结果表明,改变神经干细胞的内在信号通路(如PTEN)可以提高它们的治疗效果,为未来脊髓损伤的再生策略提供了潜在的途径。

https://orcid.org/0000-0003-2233-9569 (Byung Gon Kim)

关键词: 移植轴突生长, 移植存活, 神经干细胞, PTEN, 再生, 脊髓损伤, 移植

Abstract: Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge. Here, we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation. We focused on phosphatase and tensin homolog (PTEN), a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration. By deleting Pten in mouse neural stem cells, we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture. Upon transplantation into injured spinal cords, Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution. To examine the potential influence of partial PTEN suppression, rat neural stem cells were treated with short hairpin RNA targeting PTEN, and the PTEN knockdown resulted in significant improvements in neurite growth, survival, and neurosphere motility in vitro. Transplantation of shPTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion. Moreover, PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter. These findings suggest that modifying intrinsic signaling pathways, such as PTEN, within neural stem cells could bolster their therapeutic efficacy, offering potential avenues for future regenerative strategies for spinal cord injury.

Key words: graft axon growth, graft survival, neural stem cell, PTEN, regeneration, spinal cord injury, transplantation