Yi-Jun Cai1, Lin Huang1, Tak-Yeung Leung2, Andrew Burd3. 1. Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, SAR. 2. Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR. 3. Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, SAR. Electronic address: andrewburd@surgery.cuhk.edu.hk.
Abstract
BACKGROUND AIMS: Our previous study has demonstrated the stem cell-like properties of human umbilical cord lining epithelial cells (CLECs) and their capability for epidermal reconstitution in organotypic skin culture; however, the immunogenicity of these cells has not been clearly defined. We assessed several aspects of the immune properties of CLECs in vitro. METHODS: We examined CLECs for their immunoregulatory function in a mixed lymphocyte culture experiment. We characterized the expression patterns of the major histocompatibility complex (MHC), co-stimulatory molecules and the pro-/anti-inflammatory cytokines and growth factors in CLECs by means of reverse transcription-polymerase chain reaction, Western blotting, flow cytometry and FlowCytomix multiple analyte detection assays. RESULTS: CLECs were found not to induce but to suppress the proliferation response of the peripheral blood mononuclear cells in a mixed lymphocyte culture assay. They did not express the MHC class II antigen HLA-DR but the non-classic MHC class I antigens HLA-G and HLA-E and lacked the expression of the co-stimulatory molecules CD40, CD80 and CD86. In addition, they produced less interleukin-1β and transforming growth factor-β1 but more interleukin-4 and hepatocyte growth factor than did adult keratinocytes, a pattern in favor of wound healing with less inflammation response. CONCLUSIONS: Our data suggest that CLECs have an immunosuppressive function in addition to their low immunogenicity. This could be at least partially explained by their expression of HLA-G and HLA-E molecules associated with immune tolerance and absence of HLA-DR and co-stimulatory molecules. The demonstration that CLECs produce a favorable pattern of cytokines and growth factors for wound healing provides further support for their potential clinical application in allogeneic cell therapy.
BACKGROUND AIMS: Our previous study has demonstrated the stem cell-like properties of human umbilical cord lining epithelial cells (CLECs) and their capability for epidermal reconstitution in organotypic skin culture; however, the immunogenicity of these cells has not been clearly defined. We assessed several aspects of the immune properties of CLECs in vitro. METHODS: We examined CLECs for their immunoregulatory function in a mixed lymphocyte culture experiment. We characterized the expression patterns of the major histocompatibility complex (MHC), co-stimulatory molecules and the pro-/anti-inflammatory cytokines and growth factors in CLECs by means of reverse transcription-polymerase chain reaction, Western blotting, flow cytometry and FlowCytomix multiple analyte detection assays. RESULTS: CLECs were found not to induce but to suppress the proliferation response of the peripheral blood mononuclear cells in a mixed lymphocyte culture assay. They did not express the MHC class II antigen HLA-DR but the non-classic MHC class I antigens HLA-G and HLA-E and lacked the expression of the co-stimulatory molecules CD40, CD80 and CD86. In addition, they produced less interleukin-1β and transforming growth factor-β1 but more interleukin-4 and hepatocyte growth factor than did adult keratinocytes, a pattern in favor of wound healing with less inflammation response. CONCLUSIONS: Our data suggest that CLECs have an immunosuppressive function in addition to their low immunogenicity. This could be at least partially explained by their expression of HLA-G and HLA-E molecules associated with immune tolerance and absence of HLA-DR and co-stimulatory molecules. The demonstration that CLECs produce a favorable pattern of cytokines and growth factors for wound healing provides further support for their potential clinical application in allogeneic cell therapy.
Authors: Guillaume Mestrallet; Nathalie Rouas-Freiss; Joel LeMaoult; Nicolas O Fortunel; Michele T Martin Journal: Front Immunol Date: 2021-12-06 Impact factor: 7.561