Dissection of human bodies likewise demonstrates continuity across large, multiorgan regions of the body, including the entirety of the dermis and the fascia of diverse organs and organ systems 10, 11, 12, 13.Ĭlinical disciplines including osteopathy have suggested that these connective tissue networks contain fluid and represent a body-wide communications network, akin to interstitial spaces, although this lacks detailed microscopic confirmation. More recently, the decellularization of entire fetal sheep shows that the connective tissue network is continuous throughout the body and that the connective tissue of nerves creates structural continuity between the nervous system and other tissues 3. Continuity between mesenteric fascia and the connective tissues of the small intestinal and colonic walls has also been previously recognized 6, 7, 8, 9. Multiorgan decellularization has further confirmed that ECM networks extend beyond the confines of single organs to involve neighboring structures, including thoracic (heart), abdominal (liver, gut, kidneys) and pelvic (uterus, prostate, urinary bladder) organs with their vasculature and surrounding fibrous adventitial sheaths, creating structural continuity across organ boundaries 5. These networks have biological and mechanical roles in defining the architecture and physiology of organs and, as a result, are now used as scaffolding for the creation of customized organ grafts for regenerative medicine 4. The work of Franklin Mall over a century ago 1, 2, as well as modern-day decellularization techniques 3, demonstrate that there are “reticular networks” made up of collagens, elastin, glycosaminoglycans, and other extracellular matrices (ECM) components surrounding, within, and between organs. 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. Both techniques demonstrate interstitial continuity within and between organs including within perineurium and vascular adventitia traversing organs and the spaces between them. Hyaluronic acid, a macromolecular component of interstitial spaces, was also visualized. Non-biological particles (tattoo pigment, colloidal silver) were tracked within colon and skin interstitial spaces and into adjacent fascia. Here we show evidence for continuity of interstitial spaces using two approaches. 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. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs.
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