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Identification of a Native Novel Oncolytic immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific heterodimeric Chimera of iga/igg*

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Open Journal of Preventive Medicine 2020年第6期10卷 126-150页

作者： George P. Albaugh Sudhir K. Dutta Vasantha Iyengar Samina Shami Althaf Lohani Eduardo Sainz George Kessie Prasanna Nair Sara Lagerholm Alka Kamra J.-H. Joshua Chen Shilpa Kalavapudi Rakesh Vinayek Robert Shores Laila E. Phillips Ram Nair Padmanabhan P. Nair Beltsville Human Nutrition Research Centre Agricultural Research Service Beltsville MD USA Division of Gastroenterology Sinai Hospital of Baltimore Baltimore MD USA Department of International Health Johns Hopkins University Bloomberg School of Public Health Baltimore MD USA NonInvasive Technologies LLC Elkridge MD USA Department of Pediatrics University of Maryland School of Medicine Baltimore MD USA

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to iga, about 60% of the cells expressed a novel heterodimeric iga/igg immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, iga, igg, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

关键词： Colon Epithelial Cells CXCR-4 iga/igg chimeric immunoglobulin heterodimer COX-2 LGR-5 Musashi-1 Dedifferentiation Cellular Engraftment Oncoly-sis Gastrointestinal Progenitor Stem Cells (GIP-C)

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