BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells

In this study, we demonstrated that BMP-2 induced ectopic bone marrow presents microstructure, cellularity and functional hematopoiesis, and is a fully optimized microenvironment capable of sustaining the hematopoietic stem cells and the bone marrow niche-associated CXC-chemokine-ligand-12 (CXCL12)-abundant reticular (CAR) cells, comparably to native bone marrow. BMP-2 (8 µg)/β-TCP (40 mg) was implanted subcutaneouslly into C57BL6 or Cxcl12-GFP mice. BMP-2 induced ectopic bone marrow was harvested 4 weeks after implantation and compared with femur bone marrow. Hematopoietic cells were collected from C57BL6J mice and CAR cells were collected from Cxcl12-GFP mice by collagenase digestion.