Introduction
Metastatic prostate cancer cells home to the haematopoietic stem cell (HSC) bone marrow niche. The unique signal milieu within the niche enables prostate cancer “stem cells” to evade the immune system and chemotherapy. For this reason it is anticipated that effective in vitro bone marrow niche mimics will play a significant role in the development of future prostate cancer therapies. However, effectively mimicking this complex milieu remains untenable as evidenced by the failure of existing mimics to support HSC self-renewal in vitro.
Objective
Develop an effective high-throughput in vitro bone marrow stem cell niche mimic (micro-niche), and use the micro-niche as a tool to study prostate cancer-niche interactions and as a tool to screen therapeutics.
Methods
Using a novel high-throughput microwell platform we assemble hundreds of 3D micro-niches each composed of 95 bone marrow niche stromal cells and 5 stem cells. Unlike previously reported microwell systems, our system is compatible with robotic fluidic platforms and this enables truly high-throughput screening of cancer drugs. In preliminary work we validate the quality of the micro-niche mimic by characterizing its HSC in vitro supportive capacity, and then demonstrate its utility in high-throughput drug screening.
Results
Micro-niche mimics self-assemble in microwells over the first 3-hours of culture. The micro-niche enables superior maintenance of HSC in vitro relative to gold standard cultures. The novel microwell design enables efficient high throughput screening of up to 36,000 niche mimics in a single plate.
Conclusions
The 3D micro-niche is a superior niche mimic and a promising tool for investigating prostate cancer bone marrow metastasis and drug screening.