Propagation of human prostate tissue from induced pluripotent stem cells.
Hepburn AC., Curry EL., Moad M., Steele RE., Franco OE., Wilson L., Singh P., Buskin A., Crawford SE., Gaughan L., Mills IG., Hayward SW., Robson CN., Heer R.
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.