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Sci Rep. 2018 Mar 27;8(1):4947. doi: 10.1038/s41598-018-23062-6.

Structure and Distribution of an Unrecognized Interstitium in Human Tissues.

Author information

1
Department of Medicine, Division of Digestive Diseases, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, 10003, USA.
2
Department of Medicine, Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Blvd, Hempstead, NY, 11549, USA.
3
Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
4
Department of Bioengineering and Center for Engineering MechanoBiology, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
5
Department of Pathology, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, 10003, USA.
6
Department of Pathology, New York University School of Medicine, New York, New York, 10016, USA.
7
Department of Surgery, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, 10003, USA.
8
The Center for Advanced Digestive Care, Weill Cornell Medicine, New York Presbyterian Hospital, 1305 York Avenue, 4th Floor, New York, New York, 10021, USA.
9
Department of Medicine, Division of Digestive Diseases, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, 10003, USA. neil.theise@nyumc.org.
10
Department of Pathology, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, 10003, USA. neil.theise@nyumc.org.
11
Department of Pathology, New York University School of Medicine, New York, New York, 10016, USA. neil.theise@nyumc.org.

Abstract

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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