Orthotropic Tumor Xenograft Models

Characterizing orthotopic xenograft brain tumors

Xenograft models have been an essential research tool for neuro-oncology researchers. The establishment of orthotopic xenograft brain tumors requires the injection of tumor cells into relevant neuro-anatomical sites. Monitoring the spatial distribution and growth of intracranially-implanted tumors requires non-invasive live-imaging methods such as positron emission tomography (PET). For the video below, to assist researchers at the Barrow Neurological Institute validate a novel application of a PET tracer, LifeCanvas scientists preserved, cleared, labeled, and imaged at single-cell resolution mouse brain hemispheres that harbored xenografted striatal tumors. SYTO16 (cyan) was used as a nuclear stain and DyLight 649-conjugated tomato lectin (magenta) as a vascular stain, which together highlight the tumor’s morphology.

Had researchers at the Barrow Neurological Institute not tried LifeCanvas’s state-of-the-art tissue processing pipeline and instead used conventional histological methods it would have been a far more labor-intensive and time-consuming process, only to produce an image dataset that cannot be used as flexibly as the one generated by LifeCanvas. Specifically, our volumetric imaging capabilities enabled the researchers to easily and precisely visualize their orthotopic tumors in 3D and from whichever anatomical plane they desired, providing unparalleled insight into the extent of the tumor and its effects on the brain tissue.

Furthermore, our technologies can be broadly applied to tumor tissue from various models of cancer, including cell-line based and patient-derived xenografts. As cancer researchers increasingly shift towards more complex and pathologically-relevant model systems, it is critical that methods for extracting biological information can visualize and quantify molecular and structural information in 3D and at single-cell resolution. Our SHIELD tissue preservation strategies enable multiple rounds of immunolabeling, helping capture nuanced biological information that is only accessible from highly-multiplexed studies. For example, one could imagine using our tissue clearing and imaging pipeline to characterize local invasion and distant bone or brain metastases in animal models of breast cancer, staining for the requisite markers along the way. One could additionally assess how specific drug treatments simultaneously affect the immunological landscape and matrix composition of the tumor microenvironment, overlaying each new round of data in turn and building up a rich, holistic picture of the tissue.

LifeCanvas is the only company with the tools and capabilities necessary to achieve this unprecedented advance in tissue phenotyping, with our expertise available to customers both of our devices and of our Contract Research Services arm. By working with us, the possibilities are endless.