NIH National Cancer Institute: mouse bone marrow culture yields 1.5 billion cDC1 cells per mouse in 23 days

Researchers at the National Cancer Institute, National Institutes of Health, developed a bone marrow-derived culture system that produces large numbers of highly enriched CD103-positive cDC1 cells from mice. The work was published in Myeloid Cells and reported by EurekAlert on 3 November 2026. The system is called induced cDC1, or iDC1 eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

Conventional type 1 dendritic cells (cDC1) help initiate responses against intracellular pathogens and tumors and can cross-present cell-associated antigens to CD8-positive T cells. They are rare in vivo, which makes it hard to obtain sufficient and uniform populations for mechanistic and preclinical studies eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

23-day protocol and yield

The protocol uses the cytokines FLT3L, low-dose GM-CSF and Kit ligand over 23 days. According to the authors, one mouse's bone marrow gave an estimated 1.5 billion CD103-positive cDC1 cells. More than 95% of the final culture consisted of the target cells. The reported yield was at least 75 times higher than that of previously available recombinant cytokine-based approaches eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

Compared with other bone marrow-derived dendritic cell methods, iDC1 cultures contained fewer cDC2 cells, plasmacytoid dendritic cells, macrophages and other non-target cells. Transcriptomic analyses and reference comparisons placed iDC1 cells closest to the cDC1 lineage and clearly distinct from macrophages eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

Function and mechanism

After innate immune stimulation, the cells increased expression of co-stimulatory molecules and secreted IL-12p40 and several chemokines. In functional experiments, iDC1 cells cross-presented cell-associated antigen to CD8-positive T cells. In a mouse transfer experiment, iDC1 cells supported restoration of this response in two of four cDC1-deficient recipients. The authors note that further research is needed to improve these in vivo responses eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

Mechanistic experiments identified distinct roles for the culture factors. Kit ligand and GM-CSF acted together in the early phase of cDC1 generation, while in later stages GM-CSF supported proliferation and survival. The +32 kb Irf8 enhancer, STAT5 and BRD4-associated regulatory programs contribute to efficient iDC1 generation eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.

The authors describe iDC1 as a reproducible source of relatively uniform cDC1 cells for studies of antigen processing, dendritic cell biology, vaccine research and tumor immunology. The method was developed with mouse bone marrow cells. Whether comparable approaches can be established with human cells, and whether they can support translational or clinical applications, remains to be determined eurekalert.orgEurekAlerteurekalert.orgOpen source ↗.