Defective stromal cell function in a mouse model of infusion-induced bone marrow failure

Objective To study bone marrow (BM) stromal damage in a mouse model of infusion-induced BM failure. Materials and Methods Sublethally irradiated CByB6F1 mice were infused with 5 × 106 C57BL/6 (B6) lymph node (LN) cells. Recipient BM cells were taken at 3, 7, 10, and 14 days following LN infusion and were cultured in vitro in α-modified Eagle media for 2–3 weeks. Peripheral blood and was analyzed by complete blood counts while BM lymphocyte infiltration/expansion was analyzed by flow cytometry. Marrow cells from affected and control mice were mixed and cultured in vitro to test nonspecific stromal damage. Results Donor lymphocytes infiltrated host BM within 3–7 days and expanded significantly between 7 and 10 days, concurrent with the development of leukopenia, thrombocytopenia, and marrow hypoplasia. BM cells from mice at 7, 10, and 14 days after B6-LN cell infusion were progressively defective in forming stromal feeder layers. A 1:1 mixture of BM cells from affected CByB6F1 mice and normal B6 mice failed to form an effective stromal feeder layer that could support cobblestone colony formation, indicating that lymphocytes in the BM of affected CByB6F1 mice were able to damage stromal cells in the normal B6 BM. Conclusion Activated lymphocytes destroy both hematopoietic and stromal cells as innocent bystanders in the infusion-induced BM failure model.