Large-scale production and directed induction of functional dendritic cells ex vivo from serum-free expanded human hematopoietic stem cells.

Abstract:

BACKGROUND:Dendritic cells (DCs) that are derived from hematopoietic stem cells (HSCs) are the most potent antigen-presenting cells and play a pivotal role in initiating the immune response. Hence, large-scale production and direct induction of functional DCs ex vivo from HSCs are crucial to HSC research and clinical potential, such as vaccines for cancer and immune therapy. METHODS:In a previous study, we developed a serum-free HSC expansion system (SF-HSC medium) to expand large numbers of primitive HSCs ex vivo. Herein, a DC induction and expansion medium (DC medium) was proposed to further generate large numbers of functional DCs from serum-free expanded HSCs, which were developed and optimized by factorial design and the steepest ascent method. RESULTS:The DC medium is composed of effective basal medium (Iscove's modified Dulbecco's medium [IMDM]) and cytokines (2.9 ng/mL stem cell factor [SCF], 2.1 ng/mL Flt-3 ligand, 3.6 ng/mL interleukin [IL]-1β, 19.3 ng/mL granulocyte-macrophage colony-stimulating factor [GM-CSF] and 20.0 ng/mL tumor necrosis factor-α [TNF-α]). After 10-day culture in DC medium, the maximum fold expansion for accumulated CD1a+CD11c+ DCs was more than 4000-fold, and the induced DCs were characterized and confirmed by analysis of growth kinetics, surface antigen expression, endocytosis ability, mixed lymphocyte reaction, specific cytokine secretion and lipopolysaccharide stimulation. DISCUSSION:In conclusion, the combination of DC medium and SF-HSC medium can efficiently induce and expand a large amount of functional DCs from a small scale of HSCs and might be a promising source of DCs for vaccine and immune therapy in the near future.

journal_name

Cytotherapy

journal_title

Cytotherapy

authors

Hsu SC,Lu LC,Chan KY,Huang CH,Cheng SL,Chan YS,Yang YS,Lai YT,Yao CL

doi

10.1016/j.jcyt.2019.04.059

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

755-768

issue

7

eissn

1465-3249

issn

1477-2566

pii

S1465-3249(19)30749-2

journal_volume

21

pub_type

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