中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1057-1061.doi: 10.4103/1673-5374.355761

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

小脑扁桃体下疝畸形切除的供体组织建立的脑损伤模型

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    英国北斯塔福德郡医学研究所资助

A benchtop brain injury model using resected donor tissue from patients with Chiari malformation

Jacqueline A. Tickle1, Jon Sen2, Christopher Adams3, David N. Furness3, Rupert Price4, Viswapathi Kandula4, Nikolaos Tzerakis4, Divya M. Chari2, *   

  1. 1Aston Pharmacy School, College of Health and Life Sciences, Aston University, Birmingham, UK;  2School of Medicine, Faculty of Medicine and Health Sciences, Keele University, Staffordshire, UK;  3School of Life Sciences, Keele University, Staffordshire, UK; 4Department of Neurosurgery, Royal Stoke University Hospital, Stoke-on-Trent, UK
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Divya M. Chari, DPhil., d.chari@keele.ac.uk.
  • Supported by:
    This work was funded by a grant from the North Staffordshire Medical Institute, UK (to DMC and NT). 

摘要:

使用活体动物模型来评估大脑和脊髓修复的新疗法是一个有争议的领域。活体动物模型存在伦理问题,且来源于该模型的数据在预测人类研究的结果时并不总是可靠的。复制中枢神经系统三维结构的替代模型,促进了器官型神经损伤模型的发展。然而,由于缺乏获得正常人类神经组织的可靠手段,导致对病理或死后组织的依赖,从而限制了它们的生物学应用。实验建立了一个方案,使用从Chiari畸形(又名先天性小脑扁桃体下疝畸形)患者身上手术切除的小脑扁桃体组织建立一个体外器官型的脑损伤模型。存活的组织被保存了大约2周,对主要的神经细胞类型进行检测。切片中一些主要的伤后病理学特征明显。在体外病变中放置生物材料也是可行的。因此,这项 "概念验证 "研究表明,该模型有可能替代动物组织用于神经组织工程的临床前研究。

https://orcid.org/0000-0002-7095-8578 (Divya M. Chari)

Abstract: The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation (cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.  

Key words: biomaterial, Chiari malformation, cerebellar slice, human tissue, injury model, neuroregeneration, organotypic, traumatic brain injury