Xian Wa, Duleba Marcin, Yamamoto Yusuke, Vincent Matthew, McKeon Frank
Institute of Molecular Medicine, McGovern Medical School of University of Texas Health Science Center, Houston, TX 77030, USA.
Department of Biochemistry and Molecular Biology, University of Texas McGovern Medical School, Houston, TX 77030, USA.
J Clin Med. 2018 Dec 16;7(12):555. doi: 10.3390/jcm7120555.
Autologous transplantation of human epidermal stem cells cultured in Green's method is one of the first examples of utilizing adult stem cells in regenerative medicine. Using the same method, we cloned p63-expressing distal airway stem cells and showed their essential role in lung regeneration in a mouse model of acute respiratory distress syndrome. However, adult stem cells of columnar epithelial tissues had until recently evaded all attempts at cloning. To address this issue, we developed a novel technology that enabled cloning ground-state stem cells of the columnar epithelium. The adaption of this technology to clone stem cells of cancer precursors furthered our understanding of the dynamics of processes such as clonal evolution and dominance in Barrett's esophagus, as well as for testing platforms for chemical screening. Taken together, the properties of these ground-state stem cells, including unlimited propagation, genomic stability, and regio-specificity, make them ideal for regenerative medicine, disease modeling and drug discovery.
采用格林方法培养的人表皮干细胞自体移植是再生医学中利用成体干细胞的首批实例之一。我们使用相同方法克隆了表达p63的远端气道干细胞,并在急性呼吸窘迫综合征小鼠模型中证明了它们在肺再生中的重要作用。然而,直到最近,柱状上皮组织的成体干细胞仍逃避了所有克隆尝试。为解决这一问题,我们开发了一项新技术,该技术能够克隆柱状上皮的基态干细胞。将这项技术应用于克隆癌症前体干细胞,进一步加深了我们对诸如巴雷特食管中的克隆进化和优势等过程动态的理解,同时也为化学筛选测试平台提供了帮助。综上所述,这些基态干细胞的特性,包括无限增殖、基因组稳定性和区域特异性,使其成为再生医学、疾病建模和药物发现的理想选择。