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Journal of Clinical Gastroenterology:
May/June 2003 - Volume 36 - Issue 5 - pp S84-S93
Yale University Workshop on Defining the Pathologic and Clinical Significance of Dysplasia and Metaplasia in the Gastrointestinal Tract: Editors: Martin H. Floch, A. Brian West, and Saraswathi Nair: Presentations

Coprocytobiology: On the Nature of Cellular Elements from Stools in the Pathophysiology of Colonic Disease

Nair, Padmanabhan Ph.D.; Lagerholm, Sara B.S.; Dutta, Sudhir M.D.; Shami, Samina M.S.; Davis, Kirk B.S.; Ma, Shuzhen M.D.; Malayeri, Mehran Ph.D.

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Abstract

The gastrointestinal epithelium is known to undergo constant and rapid renewal resulting in millions of cells being shed into the fecal stream every day. The conventional wisdom was that these cells disintegrate upon exfoliation and will not survive the transit through the intestinal tract. In 1990, we (P.N.) made the discovery that a significant number of these cells remain intact and viable and that they can be isolated. The implications of this important discovery became apparent when we demonstrated that these cells are exclusively of colonic origin, are anatomically representative of the entire colon, and can be used for clinical investigations of disease processes. The term coprocytobiology (CCB) was coined to encompass the broad range of applications of this new technology. The somatic cell sampling and recovery (SCSR) process involves the isolation of exfoliated colonocytes from a small sample of stool (≈1 g) collected and transported in a unique medium at ambient temperature, providing cells for the detection of a number of biomarkers of disease propensity. These exfoliated colonocytes express cytokeratins indicating epithelial lineage as well as colon-specific antigen. Over the years, the study of exfoliated colonocytes has provided striking new insights into the biology of colon cancer and inflammatory bowel disease, including detection of p53 gene mutations, reverse transcriptase polymerase chain reaction amplification, and identification of CD44 splice variants, neoplasia-associated specific binding of plant lectins, and expression of COX-2, the inducible form of cyclooxygenase. The functional diversity of cells isolated by SCSR is revealed by the demonstration of cell surface markers such as secretory component, IgA, and IgG on the one hand and the amplification and cloning of the human insulin receptor and the expression of the multidrug resistance gene mdr-1 on the other hand. This review portrays the immense potential of CCB as a powerful tool for investigating the pathophysiology of disease, identifying genetic variants in pharmacogenetics, assessment of mucosal immunity, and several other applications that use somatic cells.

Coprocytobiology (CCB), a term derived from Greek (kopros meaning excrement and kytos meaning hollow vessel), is defined as the study of the science of cellular elements from stool, both human and animal. In 1990, our observation that cells exfoliated from the gastrointestinal tract remain viable in the fecal stream and can be recovered intact from fresh stool samples reversed conventional wisdom that stool is a fecal mass of nondescript heterogeneous waste formed from degraded digested material. 1,2 Initial observations were soon followed by the development of more elegant procedures for their isolation and characterization, opening new avenues for the noninvasive study of somatic cells as sentinels of health and disease. 3,4 During the course of the last few years, CCB has been recognized as a novel approach for the noninvasive detection of colon cancer using tumor-associated biomarkers. 5-10 This presentation reviews the evolution of CCB as a concept and describes the associated technology, somatic cell sampling and recovery (SCSR), which enables the isolation of viable colonocytes from stool samples for downstream investigations into the cellular basis of disease.

© 2003 Lippincott Williams & Wilkins, Inc.

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