Walsh Ciara M, Hill Sophie, Newland Ben, Dooley Dearbhaile
School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Mater Today Bio. 2025 Aug 19;34:102211. doi: 10.1016/j.mtbio.2025.102211. eCollection 2025 Oct.
Spinal cord injury (SCI) is a devastating condition for which no curative therapy is currently available. The pathology of SCI is underscored by an inflammatory lesion at the site of injury that exacerbates damage and impedes recovery. Immunomodulation is a promising strategy for SCI repair and thus there is enhanced focus on identifying and testing novel immunotherapeutics. Efficient preclinical models are required for screening new therapies, and models can reduce the overall cost and animal numbers required for this process. Organotypic spinal cord slices offer a promising platform for modelling spinal cord pathologies as they retain the tissue architecture with the benefit of a controlled culture environment. Neuroinflammation can be induced in organotypic spinal cord slices by adding inflammatory agents to the culture system, however this results in global inflammation and lacks the heterogeneity of a focal lesion surrounded by spared tissue that is observed . To improve this model, we have applied previously characterised macroporous cryogels for localised delivery of lipopolysaccharide (LPS) in organotypic spinal cord slices. Placement of LPS-loaded cryogels adjacent to spinal cord slices increases the expression of proinflammatory CD86 in Iba-1 microglia/macrophages and decreases the expression of myelin basic protein at the lesion site. These effects are not observed distal to the cryogel, indicating the formation of a focal inflammatory lesion. These effects can be reversed through treatment with the immunomodulatory cytokine interleukin(IL)-13. This novel model of neuroinflammation provides an innovative platform for screening potential immunotherapeutics and improving the efficiency of future preclinical SCI studies.
脊髓损伤（SCI）是一种严重的疾病，目前尚无治愈性疗法。SCI的病理学特征是损伤部位的炎症性病变，这种病变会加剧损伤并阻碍恢复。免疫调节是SCI修复的一种有前景的策略，因此人们越来越关注新型免疫疗法的识别和测试。筛选新疗法需要有效的临床前模型，这些模型可以降低该过程所需的总体成本和动物数量。器官型脊髓切片为模拟脊髓病理提供了一个有前景的平台，因为它们保留了组织结构，且受益于可控的培养环境。通过向培养系统中添加炎症因子，可以在器官型脊髓切片中诱导神经炎症，然而，这会导致全身性炎症，并且缺乏在观察到的由未受损组织包围的局灶性病变的异质性。为了改进这个模型，我们应用了先前表征的大孔冷冻凝胶在器官型脊髓切片中局部递送脂多糖（LPS）。将负载LPS的冷冻凝胶放置在脊髓切片附近，可增加Iba-1小胶质细胞/巨噬细胞中促炎CD86的表达，并降低病变部位髓鞘碱性蛋白的表达。在冷冻凝胶远端未观察到这些效应，表明形成了局灶性炎症病变。这些效应可以通过用免疫调节细胞因子白细胞介素（IL）-13治疗来逆转。这种新型神经炎症模型为筛选潜在的免疫疗法和提高未来临床前SCI研究的效率提供了一个创新平台。
