title: Human adipose-derived stem cells impair natural killer cell function and exhibit low susceptibility to natural killer-mediated lysis.
abstract: Human adipose-derived stem cells (hASCs) have been successfully used in treating numerous diseases. However, several aspects need to be considered, particularly in the context of allogeneic cell therapy. To better understand hASCs-host interactions, we studied the phenotype of hASCs and their modulatory effect on natural killer (NK) cells by using bone marrow-mesenchymal stem cells (hBM-MSCs) as a reference. The hASCs displayed a lower susceptibility to NK cell-mediated lysis and a lower expression of ligands for DNAM-1 when compared with hBM-MSCs. Moreover, here we demonstrated that hASCs and hBM-MSCs can modulate NK cells through the action of soluble factors such as indoleamine 2,3-dioxygenase. Altogether, these results suggest that for an adoptive cell therapy based on the transfer of allogeneic hASCs, the NK-hASCs crosstalk will not result in an immediate recognition of the transferred cells. Thus, hASCs may remain in the tissue long enough to balance the immune response before being cleared.
authors.affiliation: Cellerix S.A., Tres Cantos, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: DelaRosa
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Correa
authors.forename: Sara
authors.initials: S
authors.lastname: Morgado
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramírez
authors.forename: Borja
authors.initials: B
authors.lastname: del Río
authors.forename: Ramón
authors.initials: R
authors.lastname: Menta
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Lombardo
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008024:Ligands; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
chemical_list: D006680:HLA Antigens; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007376:Interleukin-2; D008024:Ligands; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma