Human embryonic stem cells are immunogenic in allogeneic and xenogeneic settings

Abstract

Recent studies have suggested that human embryonic stem cells (HESC) are immune-privileged and may thereby circumvent rejection. The expression of immunologically active molecules was studied by DNA microarray analysis and by flow cytometry. HESC were transplanted into immunologically competent mice and traced by fluorescence in-situ hybridization (FISH) and immunohistochemistry. The ability of HESC to directly and indirectly induce immune responses in CD4+ T-cells from naive and transplanted mice was studied. Their ability to induce immune responses of human CD4+ T-cells, when cultured in the presence of dendritic cells (DC) syngeneic to responder T-cells, was also analysed. HESC demonstrated expression of HLA class I and HLA class II genes, but the cell surface expression of HLA class II molecules was low even after incubation with IFNgamma. In wild-type mice, HESC could be demonstrated by FISH until 3 days after transplantation and were surrounded by heavy infiltrates of T-cells and macrophages. HESC induced a similar immune response as human fibroblast cells (HFib) on naive and immunized T-cells, both directly and in the presence of syngeneic DC. A similar response was observed in the allogeneic setting. It is concluded that HESC are immunologically inert and do not inhibit immune responses during direct or indirect antigen presentation, and they were acutely rejected in a xenogeneic setting.

Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts

“…For example, the data presented here clearly demonstrate that hESC-derived cells do not escape immune surveillance in a xenograft. Although this observation is at odds with an earlier study wherein cardiac-committed mouse ES cells were transplanted into infarcted sheep myocardium in the absence of immunosuppression [20], recent data from Swijnenburg et al [48] and Grinnemo et al [49] support our results. The use of autologous ESlike donor cells (as for example, isolated from spermatogonial stem cell cultures [50]) or alternatively the development of novel tolerance approaches [51] might circumvent this problem.…”

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

“…Another area of concern when using ESCs and fetal tissue-derived NSCs is their tumorigenicity, documented in animal experiments (35,36) and, sometimes, in clinical trials (37). Furthermore, data regarding the lack of immunogenicity of ESCs are not consistent, and they have been reported to elicit severe immune rejection (38,39).…”

Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro

“…ESCs have the potential to differentiate into any kind of body cell and can proliferate in vitro infinitely. However, they are difficult to control and have a risk for graft rejection (Grinnemo et al, 2006). Adult stem cells with multilineage differentiation capability are relatively safer in application, but are difficult to obtain in large quantities.…”

“…Several cell types have been developed from hESCs (Carpenter et al, 2001;Kehat et al, 2003;Lavon et al, 2004), though the current differentiation methods are still unsatisfactory. Additionally the risks of tumor formation and immune rejection after hESC transplantation are always a concern (Grinnemo et al, 2006).…”