Underbayev Chingiz, Kasar Siddha, Yuan Yao, Raveche Elizabeth
Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, MSB C512, Newark, NJ 07103, USA.
J Biomed Biotechnol. 2012;2012:758169. doi: 10.1155/2012/758169. Epub 2012 Apr 30.
Human disease animal models are absolutely invaluable tools for our understanding of mechanisms involved in both physiological and pathological processes. By studying various genetic abnormalities in these organisms we can get a better insight into potential candidate genes responsible for human disease development. To this point a mouse represents one of the most used and convenient species for human disease modeling. Hundreds if not thousands of inbred, congenic, and transgenic mouse models have been created and are now extensively utilized in the research labs worldwide. Importantly, pluripotent stem cells play a significant role in developing new genetically engineered mice with the desired human disease-like phenotype. Induced pluripotent stem (iPS) cells which represent reprogramming of somatic cells into pluripotent stem cells represent a significant advancement in research armament. The novel application of microRNA manipulation both in the generation of iPS cells and subsequent lineage-directed differentiation is discussed. Potential applications of induced pluripotent stem cell--a relatively new type of pluripotent stem cells--for human disease modeling by employing human iPS cells derived from normal and diseased somatic cells and iPS cells derived from mouse models of human disease may lead to uncovering of disease mechanisms and novel therapies.
人类疾病动物模型对于我们理解生理和病理过程中涉及的机制而言是绝对无价的工具。通过研究这些生物体中的各种基因异常,我们能够更好地洞察导致人类疾病发展的潜在候选基因。就此而言,小鼠是人类疾病建模中使用最广泛且最便利的物种之一。已经创建了成百上千种近交、同源和转基因小鼠模型,并且目前在全球范围内的研究实验室中得到了广泛应用。重要的是,多能干细胞在培育具有所需人类疾病样表型的新型基因工程小鼠方面发挥着重要作用。诱导多能干细胞(iPS细胞)代表着将体细胞重编程为多能干细胞,是研究手段的一项重大进展。本文讨论了微小RNA操纵在iPS细胞生成及随后的定向谱系分化中的新应用。诱导多能干细胞(一种相对新型的多能干细胞)通过利用源自正常和患病体细胞的人类iPS细胞以及源自人类疾病小鼠模型的iPS细胞进行人类疾病建模的潜在应用,可能会揭示疾病机制并带来新的治疗方法。