Khatri Mahesh, Chattha Kuldeep S
a Food Animal Health Research Program; Ohio Agricultural Research and Development Center; The Ohio State University ; Wooster , OH United States.
Virulence. 2015;6(1):40-9. doi: 10.4161/21505594.2014.983020.
In this study, we describe the isolation and characterization of epithelial stem-like cells from the swine umbilical cord and their susceptibility to influenza virus infection. Swine umbilical cord epithelial stem cells (SUCECs) expressed stem cell and pluripotency associated markers such as SSEA-1, SSEA-4, TRA 1-60 and TRA 1-81 and Oct4. Morphologically, cells displayed polygonal morphology and were found to express epithelial markers; pancytokeratin, cytokeratin-18 and occludin; mesenchymal cell markers CD44, CD90 and haematopoietic cell marker CD45 were not detected on these cells. The cells had extensive proliferation and self- renewal properties. The cells also possessed immunomodulatory activity and inhibited the proliferation of T cells. Also, higher levels of anti-inflammatory cytokine IL-10 were detected in SUCEC-T cell co-cultures. The cells were multipotent and differentiated into lung epithelial cells when cultured in epithelial differentiation media. We also examined if SUCECs are susceptible to infection with influenza virus. SUCECs expressed sialic acid receptors, used by influenza virus for binding to cells. The 2009 pandemic influenza virus and swine influenza virus replicated in these cells. SUCECs due to their differentiation and immunoregulatory properties will be useful as cellular therapy in a pig model for human diseases. Additionally, our data indicate that influenza virus can infect SUCECs and may transmit influenza virus from mother to fetus through umbilical cord and transplantation of influenza virus-infected stem cells may transmit infection to recipients. Therefore, we propose that umbilical cord cells, in addition to other agents, should also be tested for influenza virus before cryopreservation for future use as a cell therapy for disease conditions.
在本研究中，我们描述了从猪脐带中分离和鉴定上皮样干细胞及其对流感病毒感染的易感性。猪脐带上皮干细胞（SUCECs）表达干细胞和多能性相关标志物，如阶段特异性胚胎抗原-1（SSEA-1）、阶段特异性胚胎抗原-4（SSEA-4）、肿瘤相关抗原1-60（TRA 1-60）、肿瘤相关抗原1-81（TRA 1-81）和八聚体结合转录因子4（Oct4）。在形态学上，细胞呈现多边形形态，并被发现表达上皮标志物；全细胞角蛋白、细胞角蛋白-18和闭合蛋白；在这些细胞上未检测到间充质细胞标志物CD44、CD90和造血细胞标志物CD45。这些细胞具有广泛的增殖和自我更新特性。这些细胞还具有免疫调节活性，并抑制T细胞的增殖。此外，在SUCEC-T细胞共培养物中检测到较高水平的抗炎细胞因子白细胞介素-10（IL-10）。当在上皮分化培养基中培养时，这些细胞具有多能性并分化为肺上皮细胞。我们还研究了SUCECs是否易受流感病毒感染。SUCECs表达流感病毒用于结合细胞的唾液酸受体。2009年大流行性流感病毒和猪流感病毒在这些细胞中复制。由于其分化和免疫调节特性，SUCECs在猪模型中作为人类疾病的细胞治疗将是有用的。此外，我们的数据表明流感病毒可以感染SUCECs，并且可能通过脐带从母亲传播流感病毒给胎儿，并且流感病毒感染的干细胞移植可能将感染传播给接受者。因此，我们建议，除了其他制剂外，脐带细胞在冷冻保存以供将来用作疾病状况的细胞治疗之前，也应进行流感病毒检测。
