Microscopic view into the living tissue corrects mistaken understanding of 20% of the body

Standard methods to slice and fix tissues for close-up exams end up draining the interconnected chambers. The collagen-based supports around those spaces then collapse and stick together, creating the appearance of a dense, supportive tissue. Looking at the tissues live show that they are fluid filled and act as shock absorbers and have different function.

Researcher propose a revision of the anatomical concepts of the submucosa, dermis, fascia, and vascular adventitia, suggesting that, rather than being densely-packed barrier-like walls of collagen, they are fluid-filled interstitial spaces. The presence of fluid has important implications for tissue function and pathology. Our data comparing rapidly-biopsied and frozen tissue with tissue fixed in a standard fashion suggest that the spaces they describe, supported and organized by a collagen lattice, are compressible and distensible and may thus serve as shock absorbers. All of the organs in which we have detected this structure are subject to cycles of compression and distension, whether relatively constant (lungs, aorta) or intermittent (digestive tract after a meal, urinary bladder during micturition, skin under mechanical compression, fascial planes during action of the musculoskeletal system).

Typical descriptions of the interstitium suggest spaces between cells but now researches describe macroscopically visible spaces within tissues – dynamically compressible and distensible sinuses through which interstitial fluid flows around the body. Our findings necessitate reconsideration of many of the normal functional activities of different organs and of disordered fluid dynamics in the setting of disease, including fibrosis and metastasis. A submucosa subjected to directional, peristaltic flow is not the previously envisaged wall of dense connective tissue, but a potential conduit for movement of injurious agents, pro-fibrogenic signaling molecules, and tumor cells. This raises the possibility that direct sampling of the interstitial fluid could be a diagnostic tool. Finally, our study demonstrates the power of in vivo microscopy to generate fresh insights into the anatomy and physiology of normal and diseased tissues.

The interstitial space is the primary source of lymph and is a major fluid compartment in the body. While the anatomy and composition of the interstitial space between cells is increasingly understood, the existence, location, and structure of larger inter- and intra-tissue spaces is described only vaguely in the literature. This is particularly important in reference to “third spacing” (interstitial fluid build-up) and when considering overall interstitial fluid flow and volume, which have not been well studied1.

Advances in invivo microscopy offer the potential to identify new, functionally-relevant anatomical structures in humans. Lymphatic vessels in the brain, for example, were recently identified for the first time using in vivo multiphoton microscopy imaging through a thinned skull preparation

Nature Scientific Reports – Structure and Distribution of an Unrecognized Interstitium in Human Tissues

Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60–70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.


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