Poster abstracts
Poster number 91 submitted by Randall Carpenter
Spinal cord injury alters the proliferation, mobilization and retention of hematopoietic stem and progenitor cells
Randall S. Carpenter (Neuroscience Graduate Program, The Ohio State University, Columbus, OH 43212), Adrienne M. Dorrance (Division of Hematology, The Ohio State University, Columbus, OH 43212), Phillip G. Popovich (Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH 43212)
Abstract:
Spinal cord injury (SCI) causes immunological and hematological dysfunction, which impair host defense and tissue repair. Hematopoiesis is compromised in SCI patients but the mechanisms underlying this deficit are unknown. Here, an experimental mouse SCI model was used to determine the effect of SCI (or sham surgery) on hematopoietic stem/progenitor cells (HSPCs) in bone marrow, blood and spleen. In vivo bioluminescent imaging of transgenic mice expressing luciferase under a Cyclin B2 promoter revealed that bone marrow cell proliferation increases 7-14 days after SCI. Flow cytometric analysis of HSPCs purified from bone marrow revealed expansion of this cell population >1.5-fold at 7 & 28 dpi (vs. sham injury). However, a MethoCult colony forming unit (CFU) assay failed to show a corresponding increase in number of CFUs, suggesting that despite enhanced proliferation and expansion of HSPCs in bone marrow after SCI, their clonogenic potential is impaired. We also assessed the mobilization of HSPCs from bone marrow to blood and their retention/proliferation in the spleen. At 3 dpi, release of HSPCs into circulation was reduced 4-fold. In the spleen, HSPCs were reduced ~50% (vs. sham-injury) and the proliferation of residual splenic HSPCs was decreased 1.5-fold. Reduced extramedullary hematopoiesis in the spleen of SCI mice may correspond with a disruption of intraspinal sympathetic control of HSPC mobilization. In conclusion, these data are the first to show a time- and location-dependent effect of SCI on HSPCs and hematopoiesis. Future experiments will continue to investigate the underlying pathophysiological mechanisms and the immunological/hematological consequences of SCI-induced changes in hematopoiesis.
Keywords: Spinal Cord Injury, Hematopoiesis, Neuroimmunology