title: Human neural stem/progenitor cells derived from embryonic stem cells and fetal nervous system present differences in immunogenicity and immunomodulatory potentials in vitro.
abstract: To develop cell therapies for damaged nervous tissue with human neural stem/progenitor cells (hNPCs), the risk of an immune response and graft rejection must be considered. There are conflicting results and lack of knowledge concerning the immunocompetence of hNPCs of different origin. Here, we studied the immunogenicity and immunomodulatory potentials of hNPCs cultured under equivalent conditions after derivation from human embryonic stem cells (hESC-NPCs) or human fetal spinal cord tissue (hfNPCs). The expression patterns of human leukocyte antigen, co-stimulatory and adhesion molecules in hESC-NPCs and hfNPCs were relatively similar and mostly not affected by inflammatory cytokines. Unstimulated hfNPCs secreted more transforming growth factor-β1 (TGF-β1) and β2 but similar level of interleukin (IL)-10 compared to hESC-NPCs. In contrast to hfNPCs, hESC-NPCs displayed 4-6 fold increases in TGF-β1, TGF-β2 and IL-10 under inflammatory conditions. Both hNPCs reduced the alloreaction between allogeneic peripheral blood mononuclear cells (PBMCs) and up-regulated CD4(+)CD25(+)forkhead box P3 (FOXP3)(+) T cells. However, hESC-NPCs but not hfNPCs dose-dependently triggered PBMC proliferation, which at least partly may be due to TGF-β signaling. To conclude, hESC-NPCs and hfNPCs displayed similarities but also significant differences in their immunocompetence and interaction with allogeneic PBMCs, differences may be crucial for the outcome of cell therapy.
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, Stockholm, Sweden. Jia.Liu@ki.se
authors: Jia
authors: J
authors: Liu
authors: Cecilia
authors: C
authors: Götherström
authors: Magda
authors: M
authors: Forsberg
authors: Eva-Britt
authors: EB
authors: Samuelsson
authors: Jiang
authors: J
authors: Wu
authors: Cinzia
authors: C
authors: Calzarossa
authors: Outi
authors: O
authors: Hovatta
authors: Erik
authors: E
authors: Sundström
authors: Elisabet
authors: E
authors: Åkesson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005333:Fetus / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D058953:Neural Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D016753:Interleukin-10