Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential

Abstract

In this study we describe the derivation and immunological characterization of a primary epithelial cell type from the human umbilical cord membrane. These cord lining epithelial cells (CLECs) expressed and/or secreted isoforms of the nonclassical human leukocyte antigen class I (HLA-1b) glycoproteins, HLA-G and E. Conditioned media from CLECs inhibited mitogen-stimulated T-lymphocyte responses, and in a mixed leukocyte reaction (MLR) assay, cocultured CLECs inhibited allogeneic responses with a concomitant reduction in proinflammatory cytokines. Using a transwell coculture system, it was demonstrated that these immunoregulatory effects were mediated by soluble factors secreted by CLECs, in a dose-dependent manner. Functional studies using HLA-G blocking antibody showed that the effects of CLEC-secreted products could be inhibited, thus demonstrating a significant and important role for soluble HLA-G. In vivo, we show that transplanted CLECs could be maintained for extended periods in immunocompetent mice where xenorejection rapidly destroyed primary keratinocytes, a control human epithelial cell type. Additionally, CLECs delayed the rejection of keratinocytes and extended their survival when cotransplanted, indicating an ability to protect adjacent human cell types that would otherwise be rejected if transplanted alone. We also show that CLECs transduced with a modified human proinsulin gene were transplanted intraperitoneally into streptozotocin (STZ)-induced diabetic mice, resulting in significantly lower levels of serum glucose compared to control mice. This study has characterized the immunological properties of CLECs and tested a potential therapeutic application in the treatment of a type 1 diabetes mouse model.

Replication of influenza A virus in swine umbilical cord epithelial stem-like cells

“…In this study, we demonstrated that similar to human UCECs, 8 SUCECs also possess immunoregulatory properties. SUCECs significantly suppressed the proliferation of T cells in vitro in response to mitogen, suggesting that SUCECs will be valuable cell source to examine the role of these cells in a pig model of human inflammatory diseases.…”

“…Human UCECs have been isolated and characterized. 8,25,26 Similar to human UCECs, SUCECs were highly proliferative and expressed embryonic stem cell and pluripotency markers including SSEA-1, SSEA-4, TRA-1-60, TRA-1-81, and Oct-4 and showed in vitro differentiation potential. 25,26 The expression of these factors indicated that these cells possess many of the properties of embryonic cells.…”

“…6 Moreover, their collection is relatively easy and does not involve any invasive interventions. 7,8 Due to these properties, umbilical cord stem cells are being actively tested in human clinical trials as an alternative source of stem cells. 9,10 Influenza A and B viruses cause seasonal annual epidemics resulting in 3-5 million clinical cases and between 250,000-500,000 deaths annually.…”

Tissue-Cultured Human Cord Lining Epithelial Cells in Treatment of Persistent Corneal Epithelial Defect

“…CLECs were differentiated to be some type of epithelium by some invitro study [11], [12], [13]. Zhou Y, MacAry PA, et al, have shown many markers of corneal and limbal epithelial cells in CLECs and the safety of CLECs human transplantation [12], [14]. Reza HM, (2011) has differentiated CLECs to corneal epithelial cells and transplanted them to rabbit eyes.…”

Stem cell therapy for diabetes

“…Together with insulin gene transfection in vitro , after peritoneal transplantation into sterptozotocin-induced diabetic mice, there was some improvement in glucose levels. [3] Our colleagues in Singapore[45] have used another model of autologous hepatocytes from streptozotocin-induced diabetic pigs. These separated hepatocytes were successfully transfected ex-vivo with a human insulin gene construct by electrophoration, and then the cells were injected directly back into the liver parenchyma using multiple separate injections.…”