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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Fellowship

Developing a stem-cell prostate organoid model - reducing global animal usage in prostate development and cancer studies

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At a glance

Pending start
Award date
July 2022 - June 2024
Grant amount
£120,037
Principal investigator
Dr Adriana Buskin
Institute
Newcastle University

R

  • Replacement

Application abstract

BACKGROUND: Prostate cancer is the most common cancer in men, with over 47,000 new cases diagnosed every year in the UK alone. The discovery of treatments for prostate cancer has been hindered by the lack of clinically relevant human prostate models that recapitulate the full spectrum of this heterogeneous disease. Current in vitro tools, such as prostate cancer cell lines and prostate primary cells, lack the structural complexity of tumours. Other models such as animal xenografts have been used in efforts to recreate the tumour ex vivo, however these models are expensive, and the host's system is physiologically incompatible to the human setting.

OPPORTUNITY: My work has shown that human iPSC-derived prostate organoids mimic prostate tissue in vitro and they can also reconstruct the patient's cancer phenotype by the incorporation of mutations that promote the formation of prostate cancer. Our group was the first to establish a hiPSC-derived prostate organoid model using inductive urogenital mesenchymal (UGM) cells from rodents, which produces 3D layered structures faithfully resembling the human prostate and provides a new powerful tool for prostate studies. However, removing its dependence on animal tissue would be a huge advance.

AIM: I seek to develop a novel hiPSC-derived organoid model for prostate studies free of animal tissue.

PLAN: In order to establish prescribed factors, without the need for animal UGM, I recently undertook transcriptome sequencing of UGM cells to find which factors induce iPSCs towards a prostatic lineage fate. This pilot data, combined with previous work in human embryonic cells, has allowed me to design a novel animal-free differentiation protocol using hiPSCs. Through this critical research, I will replace the use of animals by generating hiPSC-derived prostate organoids and reduce the use of animal models in the field of prostate cancer, expanding the accessibility of this model to researchers across the world.