Sefiani Arthur
Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, TX, United States.
NeuroCreis, Inc., College Station, TX, United States.
Front Cell Neurosci. 2023 Aug 23;17:1253192. doi: 10.3389/fncel.2023.1253192. eCollection 2023.
The average age of a patient with neurotraumatic injuries or neurodegenerative diseases has been increasing worldwide. The preclinical live animal models used for neurotrauma and neurodegenerative diseases are typically young adults, failing to represent the age of humans in the clinic. This dichotomy in age between human populations and animal models is likely to impede the understanding of the pathological mechanisms of most neurological disorders and the translation of their respective promising therapies. This lack of cohesion between animal models and patients in the clinic begins prior to testing, it starts during the drug screening phase. Conventional screening methods typically involve the use of stem cell derived neural cells, with some researchers using embryonic derived neural cells instead. These cells lack the fundamental characteristics present in aged neural cells, such as age-induced changes in process length and branching in microglia and how astrocytes respond to various insults. Various technologies and techniques have been developed recently that can help researchers use age-appropriate neural cells for their drug discovery endeavors. The use of age-appropriate neural cells during screening phases is hypothesized to significantly increase the translation rate of the hits to the geriatric patients suffering from neurotraumatic and neurodegenerative diseases.
在全球范围内,患有神经创伤性损伤或神经退行性疾病的患者平均年龄一直在上升。用于神经创伤和神经退行性疾病研究的临床前活体动物模型通常是年轻成年动物,无法代表临床中人类的年龄。人类群体与动物模型之间的这种年龄差异可能会阻碍对大多数神经系统疾病病理机制的理解以及各自有前景疗法的转化。动物模型与临床患者之间缺乏连贯性在测试之前就已存在,始于药物筛选阶段。传统的筛选方法通常涉及使用干细胞衍生的神经细胞,一些研究人员则使用胚胎衍生的神经细胞。这些细胞缺乏老年神经细胞所具有的基本特征,例如随着年龄增长而在小胶质细胞中出现的突起长度和分支变化,以及星形胶质细胞对各种损伤的反应方式。最近已经开发出各种技术,可帮助研究人员在药物发现工作中使用与年龄相匹配的神经细胞。据推测,在筛选阶段使用与年龄相匹配的神经细胞可显著提高将筛选结果转化应用于患有神经创伤和神经退行性疾病老年患者的成功率。