Maximum intensity projection of a whole mount human precision cut liver slice (PCLS) labeled with antibodies against pan-collagen, α-smooth muscle actin and vimentin.
Over the last five years, Visikol has executed many precision cut tissue slice (PCTS) projects for clients despite the fact that we have a multitude of 2D and 3D (e.g., spheroid, organoid) cell culture models that we can use instead. The reason for this popularity is complicated, but boils down to the fact that even the best in vitro models are imperfect and tissue slice models provide a few unique features which simply are not possible in these systems.
When designing an in vitro assay with clients, the Visikol team puts a lot of focus on the specific research question at hand and work backwards towards determining which assay and model are best for that specific question. In the case of in vitro assays, we tend to do a lot of spheroid work as companies are very familiar with our various high content imaging approaches which uniquely allow our team to image these models in their entirety and to leverage them to answer novel research questions (e.g., antibody penetration, T-cell infiltration). However, a few years ago we launched a suite of precision cut tissue slice models which now include both animal and human kidney and liver tissue slice models. The reason for this addition was that we wanted to provide our clients with the broadest suite of models possible and these models meet a distinct customer need.
That need is that while we are making great strides in the advanced cell culture space, these models simply do not develop the complex physiology and structure that we see in vivo. For many research questions, this structure and innate functionality is critical and cannot be effectively replicated in current in vitro models. However, these same researchers are not able to develop effective animal models for the question at hand or want to see a different human model. It is for these cases where precision cut tissue slice models are particularly useful as they harness fresh patient or animal tissue that can be kept in culture for days-to-weeks depending on the type of tissue that is being used. These tissues are sliced into ultra-thin sections and kept functional on permeable supports (PermaCell) where various therapeutics can be tested. With human tissues, this provides a unique opportunity to test the efficacy and safety of a therapeutic in human tissues without a clinical trial in a medium throughput approach.
Precision Cut Tissue Slice Models
Though there are great benefits of these models, there are also some significant downsides which need to be taken into account when leveraging these models for assays. The first of which is that while these tissues are the innate tissue and the innate structure is generally preserved, the tissues after being removed from the body and sectioned tend to lose functionality and viability precipitously. This means that A) your desired functionality might not be present, B) the assay window for you research question could be too short at only a few days for some tissues (e.g., disease state liver tissue) and C) the single donor you evaluate might not be indicative of the whole patient population you are trying to model. Together, all of these advantages and disadvantages need to be assessed to determine which model is best for your research question. Currently, we have the following precision cut tissue slice models that our clients can leverage: