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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.

Journal of Clinical Gastroenterology: May 2003 - Volume 36 - Issue 5 - p S84–S93
Articles

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.

From NonInvasive Technologies (P.N.), Columbia; the Division of Human Nutrition, Department of International Health, Johns Hopkins University (P.N., S.L., S.S., K.D., S.M., M.M.), Baltimore; and the Division of Gastroenterology, Department of Medicine, Sinai Hospital of Baltimore (S.L., S.D.), Baltimore, Maryland.

This work was supported in part by SBIR grants R43 DK‐56567 and R44 DK‐56567 from the National Institute of Digestive Diseases and Kidney Diseases and SBIR grants R43 CA‐81799 and R44 CA‐81799 from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Address correspondence and reprint requests to Dr. Padmanabhan Nair, NonInvasive Technologies, 4520 Hemlock Cone Way, Ellicott City, Maryland 21042. E‐mail: ppn@noninvasivetech.com.

© 2003 Lippincott Williams & Wilkins, Inc.