Fig. 9: Summary of the effects of T3 transection SCI on bone marrow hematopoiesis.

Under homeostatic conditions, HSPCs undergo highly regulated and short-lived proliferation (1). When demand dictates (i.e. stress, trauma, infection), normal bone marrow downregulates CXCL12-CXCR4 signaling (2), allowing HSPC mobilization and extramedullary hematopoiesis (3). Homeostatic bone marrow also allows for the coordinated differentiation (4) and mobilization (5) of all leukocyte lineages, maintaining normal circulating blood leukocyte levels. T3 transection SCI, however, causes chronic bone marrow failure, including protracted proliferation (1), excessive CXCL12-CXCR4 chemotactic signaling (2), and impaired mobilization leading to the accumulation of HSPCs within the bone marrow and loss of extramedullary hematopoiesis. T3 transection SCI also causes lymphopenia by reducing lymphopoiesis (4) and sequestering mature lymphocytes in bone marrow (5).