Replicative response, immunophenotype, and functional activity of monocyte-derived versus CD34(+)-derived dendritic cells following exposure to various expansion and maturational stimuli.

Dendritic cells (DCs), generated ex vivo from blood mononuclear cells (PBMC) or CD34(+) stem cells, are being used to develop novel immunotherapies. To establish optimal DC generation, a direct comparison of the optimal cell source, culture conditions, and maturation stimuli was performed, utilizing phenotypic and functional assays as end points. Plastic adherent monocytes from PBMC were expanded in a serum-free medium (X-Vivo 10) for 7 days using GM-CSF/IL-4; CD34(+) cells were expanded for 14 days using GM-CSF/IL-4/ Flt3L, in either X-Vivo 10 alone or with albumin or autologous plasma. Expanded DC from both cell sources were matured for 7 days with CD40L or IFN-alpha/TNF-alpha. Starting from 2 x 10(7) monocytes, the optimal expansion/maturation process yielded 1.73 +/- 0.52 x 10(6) CD86(+) DC. Optimal expansion of CD34(+) cells (83.9 +/- 25.0-fold) was achieved using X-Vivo 10 with 5% plasma, matured with CD40L, and yielded 10.68 +/- 2.72 x 10(6) CD86(+) DC from 1 x 10(6) CD34(+) cells. Mature DC from PBMC or CD34(+) cells had similar enhanced expression of MHC class II HLA-DR, CD80, CD83, and CD86 and were potent stimulators of mixed lymphocyte reactions. Prior to maturation, all groups of DC actively phagocytosed apoptotic melanoma cells (approximately 50% of HLA-DR(+)). CD34(+) DC matured with CD40L or IFN-alpha/TNF-alpha had reduced phagocytic capability (34 and 31% of HLA-DR(+) DC, respectively). Similar expansion and functional activity was found using cryopreserved DC precursors, cultured in gas permeable bags. We conclude that both cell lineages produce potent mature DC, permitting exploration of the optimal clinical strategy to trigger anti-tumor immune responses in patients with malignancies.

Chen B ，Stiff P ，Sloan G ，Kash J ，Manjunath R ，Pathasarathy M ，Oldenburg D ，Foreman KE ，Nickoloff BJ ... -  《CLINICAL IMMUNOLOGY》

Transduction of CD34+ cells with lentiviral vectors enables the production of large quantities of transgene-expressing immature and mature dendritic cells.

Salmon P ，Arrighi JF ，Piguet V ，Chapuis B ，Zubler RH ，Trono D ，Kindler V ... -  《JOURNAL OF GENE MEDICINE》

Differential effects of autologous serum on CD34(+) or monocyte-derived dendritic cells.

Loudovaris M ，Hansen M ，Suen Y ，Lee SM ，Casing P ，Bender JG ... -  《journal of hematotherapy & stem cell research》

Multiple signals are required for maturation of human dendritic cells mobilized in vivo with Flt3 ligand.

Mosca PJ ，Hobeika AC ，Colling K ，Clay TM ，Thomas EK ，Caron D ，Lyerly HK ，Morse MA ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》

Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes.

Pickl WF ，Majdic O ，Kohl P ，Stöckl J ，Riedl E ，Scheinecker C ，Bello-Fernandez C ，Knapp W ... -  《JOURNAL OF IMMUNOLOGY》