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

Abstract

The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and 350,000 deaths recorded annually worldwide. Benign prostatic hyperplasia (BPH), characterised by the continuous enlargement of the adult prostate, symptomatically afflicts around 50% of men worldwide. A better understanding of the biological processes underpinning these diseases is needed to generate new treatment approaches. Developmental studies of the prostate have shed some light on the processes essential for prostate organogenesis, with many of these up- or downregulated genes expressions also observed in prostate cancer and/or BPH progression. These insights into human disease have been inferred through comparative biological studies relying primarily on rodent models. However, directly observing mechanisms of human prostate development has been more challenging due to limitations in accessing human foetal material. Induced pluripotent stem cells (iPSCs) could provide a suitable alternative as they can mimic embryonic cells, and iPSC-derived prostate organoids present a significant opportunity to study early human prostate developmental processes. In this review, we discuss the current understanding of prostate development and its relevance to prostate-associated diseases. Additionally, we detail the potential of iPSC-derived prostate organoids for studying human prostate development and disease.

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

“…Through their ability to differentiate into various cell types, including those found in tumors, iPSCs can be employed to generate specific cell populations that mimic the early stages of cancer development [ 533 , 539 , 592 ]. By studying the molecular changes and aberrant signaling pathways present in these iPSC-derived cancer cells, researchers can gain valuable insights into the early detection and diagnosis of cancer [ 267 , 554 , 593 ]. This knowledge can then be translated into the development of innovative diagnostic tools and biomarkers for improved cancer screening and early intervention [ 125 ].…”

Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research

“…The organoid technology appears to be a promising research model for human science advances as these 3D cellular structures can partially mimic the organs' morphology and function. This technology has been used to study several tissues and organs, including the brain (revised in Koo et al, 2019), pancreas (revised in Boj et al, 2016), liver (revised in Huch et al, 2015), kidney (Lawlor et al, 2021), prostate (Buskin et al, 2021), female (revised in Rawlings et al, 2021), and male reproductive tissues (revised in Alves-Lopes & Stukenborg, 2018). These 3D structures have been extensively used in basic research, to better understand the physiopathology of many organs.…”

“…While ESCs are pluripotent stem cells isolated from the inner mass of blastocysts, ASCs are multipotent or unipotent stem cells from adult tissues (Cyr & Pinel, 2022). Induced pluripotent stem cells (iPSCs) are also used being adult cells reprogrammed back into an embryonic‐like pluripotent state that enables the development of any type of human cell (Buskin et al, 2021).…”

Human prostate organoid generation and the identification of prostate development drivers using inductive rodent tissues

“…The intricacies of prostate development have yet to be completely elucidated; however, drivers of the process are continually uncovered using innovative methods. Further interrogation of the developing prostate will not only benefit our knowledge of development, but may also provide some insights into prostate diseases, such as prostate cancer and benign prostatic hyperplasia (BPH), given that similarities have been observed between the molecular and histological profiles of developing and diseased prostates ( Buskin et al, 2021 ). It is of particular interest to increase understanding of developmental pathways that may be reactivated in the growth-quiescent mature prostate, leading to disease.…”

“…One of the earliest concepts linking prostate development and disease was proposed by John McNeal ( McNeal, 1978 ), who hypothesised that signalling pathways that are primarily active during prostate development, specifically in the stroma, become reactivated during adulthood leading to BPH. This idea of ‘embryonic reawakening’ may also apply to some forms of prostate cancer that share similarities in molecular profiles ( Schaeffer et al, 2008 ; Pritchard et al, 2009 ; Buskin et al, 2021 ). The hypothesis suggests that the BPH stroma is inductive and that the adult epithelium is responsive to the inductive cues ( Cunha, 2008 ).…”