Spinal cord injury causes chronic bone marrow failure

Randall S. Carpenter, Jessica M. Marbourg, Faith H. Brennan, Katherine A. Mifflin, Jodie C. E. Hall, Roselyn R. Jiang, Xiaokui M. Mo, Malith Karunasiri, Matthew H. Burke, Adrienne M. Dorrance and Phillip G. Popovich ()
Additional contact information
Randall S. Carpenter: The Ohio State University
Jessica M. Marbourg: The Ohio State University
Faith H. Brennan: The Ohio State University
Katherine A. Mifflin: The Ohio State University
Jodie C. E. Hall: The Ohio State University
Roselyn R. Jiang: The Ohio State University
Xiaokui M. Mo: The Ohio State University
Malith Karunasiri: The Ohio State University
Matthew H. Burke: The Ohio State University
Adrienne M. Dorrance: The Ohio State University
Phillip G. Popovich: The Ohio State University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marrow hematopoietic stem and progenitor cells (HSPC), but these cells cannot leave the bone marrow, even after challenging the host with a potent inflammatory stimulus. Sequestration of HSPCs in bone marrow after SCI is linked to aberrant chemotactic signaling that can be reversed by post-injury injections of Plerixafor (AMD3100), a small molecule inhibitor of CXCR4. Even though Plerixafor liberates HSPCs and mature immune cells from bone marrow, competitive repopulation assays show that the intrinsic long-term functional capacity of HSPCs is still impaired in SCI mice. Together, our data suggest that SCI causes an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction.

Date: 2020
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DOI: 10.1038/s41467-020-17564-z

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