Using Organotypic Tissue Slices to Investigate the Microenvironment of Pancreatic Cancer: Pharmacotyping and Beyond

Abstract

Organotypic tissue slices prepared from patient tumors are a semi-intact ex vivo preparation that recapitulates many aspects of the tumor microenvironment (TME). While connections to the vasculature and nervous system are severed, the integral functional elements of the tumor remain intact for many days during the slice culture. During this window of time, the slice platforms offer a suite of molecular, biomechanical and functional tools to investigate PDAC biology. In this review, we first briefly discuss the development of pancreatic tissue slices as a model system. Next, we touch upon using slices as an orthogonal approach to study the TME as compared to other established 3D models, such as organoids. Distinct from most other models, the pancreatic slices contain autologous immune and other stromal cells. Taking advantage of the existing immune cells within the slices, we will discuss the breakthrough studies which investigate the immune compartment in the pancreas slices. These studies will provide an important framework for future investigations seeking to exploit or reprogram the TME for cancer therapy.

Emerging metabolomic tools to study cancer metastasis

“…Ex vivo tissue culture Tissue biopsies are routinely used for the diagnosis of malignant and benign tumors. Tissue biopsies have emerged as a model for metabolic phenotyping studies as it often represents the entire complex structure of the TME and thus is a potential tool for disease screening, prognosis, and diagnosis [65,66]. Recently, ex vivo culture methods have significantly evolved, especially for tissue preparation and models of tumor tissue culture [67].…”

Precision-Cut Tumor Slices (PCTS) as an Ex Vivo Model in Immunotherapy Research

“…PCTS can usually retain their viability as well as the same histological, architectural, and phenotypical characteristics as the original tumor for an average of 6–7 days, depending on tumor type [ 3 , 4 , 18 , 31 , 33 , 34 ]. Thus, the ex vivo testing of therapeutic agents on PCTS can occur generally within this timeframe.…”

Microindentation of fresh soft biological tissue: A rapid tissue sectioning and mounting protocol

“…The parameters used for fresh tissue sectioning and mounting of these tissue sections for mechanical testing vary widely in literature as shown in Table 1 . The structural and compositional heterogeneity that exists within biological tissue samples adds an additional element of complexity to these tasks [ 12 , 13 ]. For example, fresh biological tissue is difficult to section as it can tear easily, resulting in damage to the structure of the tissue [ 10 , 14 ].…”