Abstract
Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether these interstitial spaces are continuous through the body or discontinuous, confined within individual organs, remains unclear. Here we show evidence for continuity of interstitial spaces using two approaches. Non-biological particles (tattoo pigment, colloidal silver) were tracked within colon and skin interstitial spaces and into adjacent fascia. Hyaluronic acid, a macromolecular component of interstitial spaces, was also visualized. Both techniques demonstrate interstitial continuity within and between organs including within perineurium and vascular adventitia traversing organs and the spaces between them. We suggest that there is a body-wide network of fluid-filled interstitial spaces that has significant implications for molecular signaling, cell trafficking, and the spread of malignant and infectious disease.
Highlights
Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs
We use HA binding protein (HABP) staining to show that interstitial spaces are continuous between tissue compartments and fascial planes in the colon, skin, and liver, as well as within the fibrous tissues around blood vessels and nerves
The movement of pigment particles could occur via macrophage engulfment and migration, our data suggest that this is unlikely
Summary
Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. It has further been shown that other fibrous tissues, including the submucosae of all other visceral organs and the subcutaneous fascia, are structurally similar, and hypothesized that they likewise support fluid flow. In all of these tissues, the spaces were defined by a network of collagen bundles 20–70 μm in diameter. In vivo endomicroscopy has shown that musculoskeletal fascia includes similar large-caliber fluid-filled spaces[17] It remains unclear, whether these interstitial compartments are continuous through the body or represent discontinuous fluidfilled channels confined within individual organs. The second examined the distribution of hyaluronic acid (HA), a macromolecular component of the smallest interstitial spaces (i.e., between cells and around capillaries) as well as the larger fibroconnective tissue spaces we recently identified[14,18,19,20]
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