中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1271-1272.doi: 10.4103/1673-5374.327345

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

靶标移植视网膜细胞的集体行为作为改善细胞整合的策略

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Targeting collective behaviors of transplanted retinal cells as a strategy to improve cellular integration

Miles Markey, Maribel Vazquez*   

  1. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Maribel Vazquez, ScD, maribel.vazquez@rutgers.edu.
  • Supported by:
    This work was supported by the US National Science Foundation (NSF CBET 180441 and 0939511) (to MV). 

摘要: Neural Regen Res:促进替代细胞间凝聚力以增强细胞整合将丰富移植策略
再生医学旨在通过用健康、功能性的干细胞替换受损的视网膜神经元来恢复视力。先前的研究已经证明前体细胞、祖细胞和成体间充质干细胞能够在体内安全移植,而没有致瘤能力。人类视网膜是一个高度细胞化的结构,有数百万个细胞分布在最大厚度为 250 m的范围内。外部的非神经组织称为视网膜色素上皮,这是一个单细胞层,有助于调节营养物质的流动、运输废物和缓解氧化应激。神经视网膜包含数百万个神经元和神经胶质,它们通过三个核层突触互连。当入射光被外核层的杆状和锥状光感受器吸收并转换成电信号时,就会发生视觉。视杆/视锥细胞随后与内核层的次级神经元(如双极细胞、水平细胞和无长突细胞)形成突触,这些细胞又与神经节层中的细胞形成网络,从而将信号沿视神经传递至视觉皮层。这个复杂网络的任何部分的神经元受损都会导致渐进式视力丧失,使用当前的治疗方案是无法治愈的。现代细胞替代疗法已将干细胞样细胞直接移植到受损的视网膜中,细胞必须迁移到损伤部位,适当分化为特化的神经元,并在天然细胞网络中形成突触以恢复视力。
来自美国新泽西州立大学的Maribel Vazquez团队已经开发出微流体系统来检查替代细胞对多种因素和刺激的集体和个体行为。微流体系统是高度可定制的体外分析,特征长度小于1 mm。微流控尺度高度适用于视网膜细胞的研究和细胞替代治疗过程中所需的迁移尺度。他们的实验室最近开发了一个微系统来模拟视柄的体内几何形状。整个设备比硬币小,并且可以很容易地使用弹性模制法制造成特征长度小于 100 m。该装置可以在一侧接种细胞和基质,并用于在精确条件下观察穿过中央通道阵列的迁移。可以在微流体模型中对发育中观察到的集体行为进行建模,以便对内聚力在移植细胞迁移中的作用进行定量研究。这些数据进一步表明了去/分化视网膜细胞迁移的最佳簇大小,这可能与 N-钙粘蛋白激活相关,需要进一步研究。
   文章在《中国神经再生研究(英文版)》杂志2022年 6 月 6  期发表。

Abstract: Introduction: The rapidly growing field of regenerative medicine incorporates fundamental principles of stem cell biology and biomedical engineering to repair tissues damaged by genetic disorder, degeneration, or traumatic injury. The global market for stem cell therapies is expanding at an accelerating rate and projected to triple to over 100 Billion USD by the end of the decade (No author listed, 2019), as per Figure 1A. However, the full market and health potential of regenerative therapies depends upon successful clinical translation of contemporary treatments, such as cell replacement therapy. Replacement strategies offer newfound promise to treat vision loss caused by degeneration of the retina, a photosensitive tissue that lines the back of the human eye to convert light into bioelectrical signals for vision. Retinal disorders, such as macular degeneration and diabetic retinopathy, are leading causes of irreversible blindness in adults and are projected to increase in prevalence in the coming decades (GBD 2019 Blindness and Vision Impairment Collaborators, 2021). Emerging cell replacement strategies (No author listed, 2019; GBD 2019 Blindness and Vision Impairment Collaborators and Vision Loss Expert Group of the Global Burden of Disease Study, 2021) showcase innovative treatments for vision loss that will dramatically increase the current market share for retinal therapeutics.