Decellurization Technique Enhances Study of ECM Structure

A new method has been developed that allows complete removal of cells from within organs of the body to enhance the study of extracellular membrane (ECM) composition and structure.

ECM is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Differing mechanical properties in ECM exert effects on both cell behavior and gene expression. ECM can exist in varying degrees of stiffness and elasticity, from soft brain tissues to hard bone tissues. The elasticity of the ECM can differ by several orders of magnitude. This property is primarily dependent on collagen and elastin concentration, and it has recently been shown to play an influential role in regulating numerous cell functions.

Investigators at the University of Copenhagen (Denmark) reported in the June 12, 2017, online edition of the journal Nature Medicine that they had developed a fast and efficient approach to enhance the study of ECM composition and structure. Termed in situ decellularization of tissues (ISDoT), it allows whole organs to be decellularized, leaving native ECM architecture intact. These three-dimensional decellularized tissues can be studied using high-resolution fluorescence and second harmonic imaging, and can be used for quantitative proteomic interrogation of the ECM.

The investigators performed high-resolution sub-micron imaging of matrix topography in normal tissue and over the course of primary tumor development and progression to metastasis in mice. Results of these studies provided the first detailed imaging of the metastatic niche. Furthermore, these data showed that cancer-driven ECM remodeling was organ specific, and that it was accompanied by comprehensive changes in ECM composition and topological structure. The investigators also described differing patterns of basement-membrane organization surrounding different types of blood vessels in healthy and diseased tissues.

The investigators stated that their method was superior to other methods tested in its ability to preserve the structural integrity of the ECM, facilitate high-resolution imaging, and quantitatively detect ECM proteins.

"We have developed a technique to obtain intact organ scaffolds and to image them using microscopes. We are the first to image the structures of primary and metastatic tumors as well as healthy organs in this way," said senior author Dr. Janine Erler, professor in the biotech research and innovation center at the University of Copenhagen. "We are now re-introducing cells into our extracellular matrix scaffolds, bringing them back to life, to study how tumors form and how cancer progresses. This is extremely exciting and offers a unique opportunity to study how cells behave in their native environment."

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