Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States of America.
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America.
PLoS One. 2020 Dec 7;15(12):e0242426. doi: 10.1371/journal.pone.0242426. eCollection 2020.
Cell culture is widely utilized to study the cellular and molecular biology of different neuronal cell populations. Current techniques to study enriched neurons in vitro are primarily limited to embryonic/neonatal animals and induced pluripotent stem cells (iPSCs). Although the use of these cultures is valuable, the accessibility of purified primary adult neuronal cultures would allow for improved assessment of certain neurological diseases and pathways at the cellular level. Using a modified 7-step immunopanning technique to isolate for retinal ganglion cells (RGCs) and amacrine cells (ACs) from adult mouse retinas, we have successfully developed a model of neuronal culture that maintains for at least one week. Isolations of Thy1.2+ cells are enriched for RGCs, with the isolation cell yield being congruent to the theoretical yield of RGCs in a mouse retina. ACs of two different populations (CD15+ and CD57+) can also be isolated. The populations of these three adult neurons in culture are healthy, with neurite outgrowths in some cases greater than 500μm in length. Optimization of culture conditions for RGCs and CD15+ cells revealed that neuronal survival and the likelihood of neurite outgrowth respond inversely to different culture media. Serially diluted concentrations of puromycin decreased cultured adult RGCs in a dose-dependent manner, demonstrating the potential usefulness of these adult neuronal cultures in screening assays. This novel culture system can be used to model in vivo neuronal behaviors. Studies can now be expanded in conjunction with other methodologies to study the neurobiology of function, aging, and diseases.
细胞培养广泛用于研究不同神经元细胞群体的细胞和分子生物学。目前,体外研究富集神经元的技术主要限于胚胎/新生动物和诱导多能干细胞(iPSCs)。尽管这些培养物的使用具有价值,但纯化的成年神经元培养物的可及性将允许在细胞水平上更好地评估某些神经疾病和途径。我们使用改良的 7 步免疫淘选技术从成年小鼠视网膜中分离视网膜神经节细胞(RGCs)和无长突细胞(ACs),成功开发了一种至少维持一周的神经元培养模型。Thy1.2+细胞的分离富含 RGCs,分离细胞的产量与小鼠视网膜中 RGC 的理论产量一致。也可以分离两种不同群体(CD15+和 CD57+)的 ACs。培养中的这三种成年神经元群体是健康的,在某些情况下,神经突的生长长度大于 500μm。优化 RGC 和 CD15+细胞的培养条件表明,神经元存活和神经突生长的可能性与不同的培养基呈反比。不同浓度的嘌呤霉素连续稀释可剂量依赖性地减少培养的成年 RGC,表明这些成年神经元培养物在筛选测定中具有潜在的用途。这种新的培养系统可用于模拟体内神经元行为。现在可以结合其他方法学来扩展研究,以研究功能、衰老和疾病的神经生物学。