Hepburn Anastasia C, Curry Emma L, Moad Mohammad, Steele Rebecca E, Franco Omar E, Wilson Laura, Singh Parmveer, Buskin Adriana, Crawford Susan E, Gaughan Luke, Mills Ian G, Hayward Simon W, Robson Craig N, Heer Rakesh
Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
Acute Internal Medicine, University Hospital of North Tees, Stockton on Tees, UK.
Stem Cells Transl Med. 2020 Jul;9(7):734-745. doi: 10.1002/sctm.19-0286. Epub 2020 Mar 14.
Primary culture of human prostate organoids and patient-derived xenografts is inefficient and has limited access to clinical tissues. This hampers their use for translational study to identify new treatments. To overcome this, we established a complementary approach where rapidly proliferating and easily handled induced pluripotent stem cells enabled the generation of human prostate tissue in vivo and in vitro. By using a coculture technique with inductive urogenital sinus mesenchyme, we comprehensively recapitulated in situ 3D prostate histology, and overcame limitations in the primary culture of human prostate stem, luminal and neuroendocrine cells, as well as the stromal microenvironment. This model now unlocks new opportunities to undertake translational studies of benign and malignant prostate disease.
人前列腺类器官和患者来源异种移植的原代培养效率低下,且获取临床组织的途径有限。这阻碍了它们在转化研究中用于确定新的治疗方法。为克服这一问题,我们建立了一种互补方法,即利用快速增殖且易于处理的诱导多能干细胞在体内和体外生成人前列腺组织。通过使用与诱导性泌尿生殖窦间充质的共培养技术,我们全面再现了原位3D前列腺组织学,并克服了人前列腺干细胞、管腔细胞和神经内分泌细胞以及基质微环境原代培养中的局限性。这种模型现在为开展良性和恶性前列腺疾病的转化研究带来了新机遇。