Transplanted spleen stromal cells with osteogenic potential support ectopic myelopoiesis

Spleen stromal lines which support in vitro hematopoiesis are investigated for their lineage origin and hematopoietic support function in vivo. Marker expression and gene profiling identify a lineage relationship with mesenchymal stem cells and perivascular reticular cells described recently in bone marrow. Stromal lines commonly express Cxcl12, Pdgfra and Pdgfr typical of bone marrow derived perivascular reticular cells but reflect a unique cell type in terms of other gene and marker expression. Their classification as osteoprogenitors is confirmed through ability to undergo osteogenic, but not adipogenic or chondrogenic differ- entiation. Some stromal lines were shown to form ectopic niches for HSCs following engraft- ment under the kidney capsule of NOD/SCID mice. The presence of myeloid cells and a higher representation of a specific dendritic-like cell type over other myeloid cells within grafts was consistent with previous in vitro evidence of hematopoietic support capacity. These studies reinforce the role of perivascular/perisinusoidal reticular cells in hematopoie- sis and implicate such cells as niches for hematopoiesis in spleen.This work was supported by project grants to HO from the Australian Research Council (#DP130101703) and the National Health and Medical Research Council of Australia (#585443). JT was supported by a CJ Martin Fellowship from the National Health and Medical Research Council of Australia. PP and HL were supported by Australian National University Postgraduate Scholarship