Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*

• 作者: Alka Kamra Althaf Lohani Eduardo Sainz George Kessie George P. Albaugh J.-H. Joshua Chen Laila E. Phillips Padmanabhan P. Nair Prasanna Nair Rakesh Vinayek Ram Nair Robert Shores Samina Shami Sara Lagerholm Shilpa Kalavapudi Sudhir K. Dutta Vasantha Iyengar
• 来源期刊: 预防医学期刊(英文)
• 学科: 地球科学
• 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)
• 年，卷（期）: yfyxqkyw_2020,（6）
• 页码范围: 126-150
• 页数: 25页
• 分类号: X70

摘要

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.