Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, California.
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa.
Am J Physiol Lung Cell Mol Physiol. 2020 Apr 1;318(4):L671-L683. doi: 10.1152/ajplung.00456.2019. Epub 2020 Feb 19.
Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung, where ferrets provide an attractive mammalian model of both acute and chronic lung diseases, such as influenza, cystic fibrosis, A1A emphysema, and obliterative bronchiolitis, closely recapitulating disease pathogenesis, as it occurs in humans. As such, ferrets have the potential to be a valuable preclinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multilineage differentiation, and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.
雪貂是多种疾病,特别是肺部、肝脏、大脑和肾脏疾病的一种有吸引力的哺乳动物模型。由于大小和细胞解剖结构的差异,许多慢性人类疾病在啮齿动物中很难建模。这在肺部尤其如此,雪貂提供了一种急性和慢性肺部疾病(如流感、囊性纤维化、A1A 肺气肿和闭塞性细支气管炎)的有吸引力的哺乳动物模型,非常接近疾病的发病机制,就像在人类中一样。因此,雪貂有可能成为评估用于肺再生的基于细胞的治疗方法的有价值的临床前模型,可能还有其他组织。诱导多能干细胞(iPSCs)为提供足够的自体细胞提供了一个很好的选择,以使患者特异性细胞治疗成为现实。不幸的是,它们尚未成功地从雪貂中创建。在这项研究中,我们证明了能够生成反映人类 iPSCs 初始多能状态的雪貂 iPSCs。雪貂胎儿成纤维细胞被重编程并获得了多能性的核心特征,具有自我更新、多谱系分化以及在转录和蛋白质水平上高水平表达核心多能性基因和途径的能力。总之,我们已经生成了雪貂多能干细胞,这为我们提高评估雪貂自体细胞移植能力提供了机会。