Transplanted spleen stromal cells with osteogenic potential support ectopic myelopoiesis

• Published in: PloS one 2019-10, Vol.14 (10), p.e0223416-e0223416
• Main Authors: O'Neill, Helen C, Lim, Hong K, Periasamy, Pravin, Kumarappan, Lavanya, Tan, Jonathan K H, O'Neill, Terence J
• Format: Article
• Language: English
• Subjects: Adipogenesis - genetics; Animals; Antigens; Biology and Life Sciences; Biomarkers; Biomedical materials; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cell Differentiation; Computational Biology - methods; Criminal investigation; CXCL12 protein; EDTA; Gene expression; Gene Expression Profiling; Genes; Genetic aspects; Grafts; Health aspects; Hematopoiesis; Hematopoiesis, Extramedullary; Hematopoietic Stem Cells - cytology; Heparan sulfate; In vivo methods and tests; Kidneys; Medicine; Medicine and Health Sciences; Mesenchyme; Mice; Mice, Inbred NOD; Mice, SCID; Myeloid cells; Myelopoiesis; Myelopoiesis - genetics; Osteogenesis; Osteosarcoma; Platelet-derived growth factor; Research and Analysis Methods; Spleen; Spleen - cytology; Stem cell transplantation; Stem cells; Stromal cells; Stromal Cells - cytology; Stromal Cells - transplantation; Tissue engineering; Transcriptome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223416

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 differentiation. Some stromal lines were shown to form ectopic niches for HSCs following engraftment 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 hematopoiesis and implicate such cells as niches for hematopoiesis in spleen.