Tickle Jacqueline A, Sen Jon, Adams Christopher, Furness David N, Price Rupert, Kandula Viswapathi, Tzerakis Nikolaos, Chari Divya M
Aston Pharmacy School, College of Health and Life Sciences, Aston University, Birmingham, UK.
School of Medicine, Faculty of Medicine and Health Sciences, Keele University, Staffordshire, UK.
Neural Regen Res. 2023 May;18(5):1057-1061. doi: 10.4103/1673-5374.355761.
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.
使用活体动物模型来测试脑和脊髓修复的新疗法是一个存在争议的领域。活体动物模型存在相关的伦理问题以及关于人类反应可预测性的科学问题。能够复制中枢神经系统三维结构的替代模型促使了器官型神经损伤模型的发展。然而，缺乏获取正常人类神经组织的可靠方法导致人们依赖病理或死后组织，这限制了它们的生物学效用。我们已经建立了一种方案，使用从Chiari畸形患者（小脑向枕骨大孔疝出，伴有异位而非病变组织）手术切除的供体小脑扁桃体组织来开发创伤性脑损伤的体外器官型模型。存活组织维持了大约两周，检测到了所有主要的神经细胞类型。可以将创伤性损伤引入切片中，损伤后病理的一些主要特征很明显。生物材料也可以放置在体外损伤部位。因此，这项“概念验证”研究表明，该模型有潜力作为在神经组织工程临床前测试中替代使用动物组织的方法。据我们所知，这是首次证明来自Chiari畸形患者的供体组织可用于开发创伤性脑损伤的台式模型。然而，在组织的临床可用性方面遇到了重大挑战，并且我们讨论了模型扩大规模时必须考虑的后勤问题。
