High-throughput propagation of human prostate tissue from induced-pluripotent stem cells

Abstract

Primary culture of human prostate organoids is slow, inefficient and laborious. To overcome this, we demonstrate a new high-throughput model where rapidly proliferating and easily handled induced pluripotent stem cells, for the first time, enable generation of human prostate tissue in vivo and in vitro.Using a co-culture technique with urogenital sinus mesenchyme, we recapitulated the in situ prostate histology, including the stromal compartment and the full spectrum of epithelial differentiation. This approach overcomes major limitations in primary cultures of human prostate stem, luminal and neuroendocrine cells, as well as the stromal microenvironment. These models provide new opportunities to study prostate development, homeostasis and disease.

A Review of Prostate Organogenesis and a Role for iPSC-Derived Prostate Organoids to Study Prostate Development and Disease

“…Microarray analyses on rodent prostate at various stages of develop-ment have produced developmental signatures that are also enriched in various grades of PCa [ 125 , 126 ]. Embryonic stem cell gene signatures have also been detected in and asso-ciated with PCa progression [ 127 , 128 , 129 ]. In some cases, specific genes have been linked to both prostate development and prostate diseases.…”

“…This dataset contains 15 tumour samples and 15 normal prostate samples. In addition to the three datasets above, we used bulk RNA-seq data of prostate derived-iPSCs [ 129 ], which we refer as embryonic prostate.…”

Engineering Prostate Cancer from Induced Pluripotent Stem Cells—New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies

“…Unlike primary cultures, iPSCs are capable of sustained self-renewal, providing unlimited cell source to investigate diseases, at molecular, cellular and functional levels. Successful reprogramming of prostate tissue and prostate-directed differentiation of iPSCs has been demonstrated, providing scope for such studies in the prostate field [69,70]. Many differentiation protocols towards 2D disease-relevant cell types have been described [71][72][73][74][75][76].…”

“…Recently, a high throughput model of generating human prostate organoids from iPSCs has also been described, involving co-culturing iPSCs with rodent urogenital sinus mesenchyme (UGM). This simple differentiation protocol results in glandular structures in vitro that faithfully mimic prostate tissue histology and express key prostate markers such as AR, prostate specific homeobox protein NKX3.1 and secretory prostate specific antigen (PSA) [69]. This approach built on previous data showing the generation of prostate tissue in xenograft studies from ESCs [118].…”

“…Effective treatment development for prostate cancer is hampered by the lack of patient-specific in vitro models that accurately recapitulate this disease. The prostate-derived iPSC generation of human prostate tissue both in vivo and in vitro is a new complimentary approach to established primary culture and PDX models [69]. Together with genome editing technologies such as CRISPR/Cas9, this model opens up new avenues to recreate the genetic make-up of individual patients and correlate drug sensitivity in vitro in a personalised fashion.…”