Background

At my home lab, we established several human bladder microtissue models to understand host-uropathogen interactions in patient-like scenarios, to be tested for novel urinary tract infections (UTI) therapeutics. However, they still lack the immune cell component, which is a crucial need for the field and a main expertise of the group of Dr. Molly Ingersoll (host). In parallel, the host lab is also implementing microfluidic models to complement their routine mouse-based studies, which can be facilitated by my knowledge in tissue bioengineering. Both labs are already aware of their respective ongoing work, with frequent communication between us. Both are also working in the urinary tract infection field and familiarized with the state-of-the-art. Moreover, the conceptual idea of incorporating immune cells in the microtissue bladder models at the home lab was already shared with the Ingersoll lab. Therefore, little introduction is expected to start the experimental procedures.

Aims

• Grow immune cells together with the human bladder tissue model developed at the home lab, so that the model has an immune component for the first time.
• Learn to isolate immune cells from human blood, identify them and keep them in culture.
• Learn the methods for examining immune cells within tissue, using histology, flow cytometry and microscopy.

Outcome

Bladder tissue models grown in the lab are built from the cells that line the bladder wall. What they lack is an immune system, and the immune response is central to how the bladder deals with infection. Adding immune cells to these models is what this stay set out to make possible.

At the host lab, Dr Carlos Flores learned to run bladder tissue on organ-on-chip devices, small units that keep tissue alive under flowing fluid so it behaves more as it would in the body. He learned to separate the urothelium, the specialised lining of the bladder, from the underlying tissue and prepare it for analysis by flow cytometry, histology and microscopy. He also learned to handle and profile immune cells, and to grow them together with bladder lining tissue. Because the experiments needed longer than a single continuous stay, he travelled between the two labs during the grant.

The techniques are now being introduced at the home lab in Bern, with the host lab still on hand when something proves difficult. Having been trained directly, the team has avoided much of the trial and error that establishing these methods usually involves.

The stay also produced working collaborations between the two labs, both on characterising immune cells within bladder tissue models and on approaches to urinary tract infections, which are currently studied largely in animals.