Abstract
We investigated the immunogenicity of allogeneic human adipose-derived mesenchymal stem cells (ADSCs) through the production of alloreactive-CD8 T and -memory CD8 T cells, based on their human leukocyte antigen (HLA) expression. In surface antigen analysis, ADSCs do not express co-stimulatory molecules, but expresses HLA-ABC, which is further increased by exposure to the pro-inflammatory cytokines as well as IFN-γ alone. For immunogenicity analysis, allogeneic ADSCs cultured in xenofree medium (XF-ADSCs) were incubated with the recipient immune cells for allogeneic–antigen stimulation. As a result, XF-ADSCs induced IFN-γ and IL-17A release by alloreactive-CD8 T cells and the production of alloreactive-CD8 T cell through a direct pathway, although they have immunomodulatory activity. In the analysis of alloreactive memory CD8 T cells, XF-ADSCs also significantly induced the production of CFSE-low-CD8 TEM and -CD8 TCM cells. However, HLA-blocking antibodies significantly inhibited the production of CFSE-low memory-CD8 T cells, indicating that HLAs are the main antigens responsible for the development of allogeneic ADSCs’ immunogenicity. These results suggested that HLA surface antigens expressed in allogeneic MSCs should be solved in order to address concerns related to the immunogenicity problem.
Highlights
Mesenchymal stem cells (MSCs), isolated originally from bone marrow aspirates, have been identified in most human tissues, including adipose tissue, umbilical cord blood, spleen, thymus and kidney [1,2,3,4,5]
This study investigated the expression of human adipose-derived mesenchymal stem cells (ADSCs) surface markers, co-stimulatory molecules, human leukocyte antigen (HLA) and NKG2DL
This study showed that XF-ADSCs have immunomodulatory effects and do not express co-stimulatory molecules, but induced IFN-γ and IL-17A release by alloreactive CD8 T cells in long-term allogeneic–antigen stimulation through a direct pathway
Summary
Mesenchymal stem cells (MSCs), isolated originally from bone marrow aspirates, have been identified in most human tissues, including adipose tissue, umbilical cord blood, spleen, thymus and kidney [1,2,3,4,5]. MSCs possess the ability to differentiate into various cell types such as osteocytes, adipocytes, neural cells, vascular endothelial cells and pancreatic β-cells and have immunomodulation and self-renewal capability [6,7,8,9,10]. The cells do not express co-stimulatory molecules such as CD40, CD80 and. Major histocompatibility complex (MHC) class I molecules are expressed at low levels and MHC class II molecules are not expressed. These are expected to induce anergy in recipient
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