Decellularized tissues as platforms for digestive system cancer models

Abstract

The extracellular matrix (ECM) is a multifunctional network of macromolecules that regulate various cellular functions and physically support the tissues. Besides physiological conditions, the ECM also changes during pathological conditions such as cancer. As tumor cells proliferate, notable changes occur in the quantity and makeup of the surrounding ECM. Therefore, the role of this noncellular component of tissues in studies of tumor microenvironments should be considered. So far, many attempts have been made to create 2-dimensional (2D) or 3-dimensional (3D) models that can replicate the intricate connections within the tumor microenvironment. Decellularized tissues are proper scaffolds that imitate the complex nature of native ECM. This review aims to summarize 3D models of digestive system cancers based on decellularized ECMs. These ECM-based scaffolds will enable us to study the interactive communication between cells and their surrounding environment which brings new potential for a better understanding of the pathophysiology of cancer.

Keywords: Cancer; Decellularized tissues; Digestive system; Extracellular matrix.

Fig. 1

A) Schematic illustration of major components found in the heterogeneous ECM network of the digestive system. B) Remodeling of ECM during colorectal cancer progression. Abnormal makeup of ECM includes elevated levels of collagen, fibronectin, and matrix enzymes such as MMPs. Immune cells are frequently recruited to the tumor site in advanced-stage tumors, facilitating the progression of cancer. With the help of proangiogenic factors, new blood vessels are formed from previous vasculature. Collagen is frequently aligned in a straight manner and positioned either parallel to the epithelium or extending perpendicularly into the tissue which facilitates the migration of tumor cells. Additionally, an increased amount of collagen, which can bind to PGs can enhance the stability of ECM components which hinders the ability of drug absorption.

Fig. 2

Process of engineering tissues through the utilization of decellularized ECM. A,B), Through the decellularization procedure, the native cells and genetic components are removed from the ECM, such as DNA, while characteristics of native tissues are preserved, C), The process of decellularization can be achieved through enzymatic, physical, or chemical methods, D), A proper characterization method is needed to confirm if the desired decellularization process is done. Common characterization techniques include extracellular and cytoplasmic components assays, cell residual assays, and observation of the general microscopic structure of decellularized ECM.

Fig. 3

Decellularized normal and tumor human colorectal tissue, A [96] and C [97]) Immunohistochemical expression of fibronectin, collagens type IV, Glycosaminoglycans(GAGs) in native and decellularized normal and tumor sections, B [96] and D [97]) Scanning Electron Microscopy (SEM) of native and decellularized normal and tumor tissue. A decrease in total proteins was observed in decellularized samples compared to native samples. The native matrix shows a homogenous surface in the SEM images, where colonic crypts are visible and the ultrastructure is preserved to a large extent in the decellularized samples.