title: Interleukin 7-engineered stromal cells: a new approach for hastening naive T cell recruitment.
abstract: In this study we determined whether human stromal cells could be engineered with a retroviral vector carrying the interleukin 7 (IL-7) gene and investigated the effects on T cells in vitro and in vivo in a murine model. Transduced mesenchymal cells strongly express CD90 (98.15%), CD105 (87.6%), and STRO-1 (86.7%). IL-7 production was 16.37 (+/-2 SD) pg/ml, which remained stable for 60 days. In vitro-immunoselected naive T cells maintained the CD45RA+ CD45RO- naive phenotype (4.2 times more than controls) after 7 days of culture with IL-7-engineered stromal cells. The apoptosis rate (4.7%) of the naive T cells cultured with transduced stromal cells overlapped with that of freshly isolated cells. Immunohistological analysis detected stromal cells in bone marrow, spleen, and thymus. Cotransplantation of IL-7-engineered stromal cells with CD34+ cells improved engraftment in terms of CD45+ cells and significantly increased the CD3+ cell count in peripheral blood, bone marrow, and spleen. These data demonstrate the following: (1) human stromal cells can be transduced, generating a normal layer; (2) transduced stromal cells in vitro maintain the naive T cell phenotype; and (3) IL-7-transduced stromal cells in vivo home to lymphoid organs and produce sufficient IL-7 in loco, supporting T cell development in a cotransplantation model. Because of their efficient cytokine production and homing, IL-7-engineered stromal cells might be an ideal vehicle to hasten immunological reconstitution in T cell-depleted hosts.
authors.affiliation: University of Perugia, 06123 Perugia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Ianni
authors.forename: Beatrice
authors.initials: B
authors.lastname: Del Papa
authors.forename: Maria
authors.initials: M
authors.lastname: De Ioanni
authors.forename: Adelmo
authors.initials: A
authors.lastname: Terenzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Sportoletti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretti
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Eugenia
authors.initials: E
authors.lastname: Gaozza
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zei
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Spinozzi
authors.forename: Claude
authors.initials: C
authors.lastname: Bagnis
authors.forename: Patrice
authors.initials: P
authors.lastname: Mannoni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Tabilio
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014161:Transduction, Genetic
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D015851:Interleukin-7; D017493:Leukocyte Common Antigens