Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, STCBM 3.200.8, San Antonio, TX, 78245, USA.
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Geroscience. 2021 Feb;43(1):115-124. doi: 10.1007/s11357-020-00284-z. Epub 2020 Oct 15.
The ability to generate in vitro cultures of neuronal cells has been instrumental in advancing our understanding of the nervous system. Rodent models have been the principal source of brain cells used in primary cultures for over a century, providing insights that are widely applicable to human diseases. However, therapeutic agents that showed benefit in rodent models, particularly those pertaining to aging and age-associated dementias, have frequently failed in clinical trials. This discrepancy established a potential "translational gap" between human and rodent studies that may at least partially be explained by the phylogenetic distance between rodent and primate species. Several non-human primate (NHP) species, including the common marmoset (Callithrix jacchus), have been used extensively in neuroscience research, but in contrast to rodent models, practical approaches to the generation of primary cell culture systems amenable to molecular studies that can inform in vivo studies are lacking. Marmosets are a powerful model in biomedical research and particularly in studies of aging and age-associated diseases because they exhibit an aging phenotype similar to humans. Here, we report a practical method to culture primary marmoset neurons and astrocytes from brains of medically euthanized postnatal day 0 (P0) marmoset newborns that yield highly pure primary neuron and astrocyte cultures. Primary marmoset neuron and astrocyte cultures can be generated reliably to provide a powerful NHP in vitro model in neuroscience research that may enable mechanistic studies of nervous system aging and of age-related neurodegenerative disorders. Because neuron and astrocyte cultures can be used in combination with in vivo approaches in marmosets, primary marmoset neuron and astrocyte cultures may help bridge the current translational gap between basic and clinical studies in nervous system aging and age-associated neurological diseases.
体外培养神经元细胞的能力对于深入了解神经系统起到了重要作用。一个多世纪以来，啮齿动物模型一直是原代培养中使用的脑细胞的主要来源，为广泛适用于人类疾病的研究提供了重要的见解。然而，在啮齿动物模型中显示出益处的治疗药物，特别是那些与衰老和与年龄相关的痴呆症有关的药物，在临床试验中经常失败。这种差异在人类和啮齿动物研究之间建立了一个潜在的“转化差距”，这至少部分可以用啮齿动物和灵长类动物之间的系统发育距离来解释。几种非人类灵长类动物（NHP）物种，包括普通狨猴（Callithrix jacchus），已被广泛用于神经科学研究，但与啮齿动物模型不同，缺乏适用于分子研究的原代细胞培养系统的实用方法，而这些方法可以为体内研究提供信息。狨猴在生物医学研究中是一种强大的模型，特别是在衰老和与年龄相关的疾病研究中，因为它们表现出与人类相似的衰老表型。在这里，我们报告了一种从医学上安乐死的出生后 0 天（P0）狨猴新生婴儿大脑中培养原代狨猴神经元和星形胶质细胞的实用方法，该方法可获得高度纯的原代神经元和星形胶质细胞培养物。可以可靠地生成原代狨猴神经元和星形胶质细胞培养物，为神经科学研究提供强大的 NHP 体外模型，从而可以对神经系统衰老和与年龄相关的神经退行性疾病进行机制研究。由于神经元和星形胶质细胞培养物可以与狨猴体内方法结合使用，因此原代狨猴神经元和星形胶质细胞培养物可能有助于弥合神经系统衰老和与年龄相关的神经退行性疾病的基础和临床研究之间当前的转化差距。
