Amy Gore, MD, PGY4 Mesenchymal Stem Cells Reverse Anemia and Bone Marrow Dysfunction Following Trauma, Shock, and Chronic Stress Department of Surgery, Division of Trauma Rutgers, The State University of New Jersey, Newark, NJ Nothing to Disclose

Injury- associated anemia EXCESSIVE HPC MOBILIZATION Loss of cells from BM ABNORMAL HPC DIFFERENTIATION Within the BM ROLE OF BONE MARROW AFTER INJURY Impaired wound healing

Unit Name Optional Presentation Title Bone Marrow Dysfunction Following Acute Injury and Hemorrhagic Shock 3 hours *p<0.05 compared to naïve Naïve as dotted line Baranski, G. et al. J Surg Res (2011) Baranski, G. et al. J Bone Marrow Res (2013) 7 days

Unit Name Optional Presentation Title HPC Mobilization Following Trauma and Shock *p<0.05 compared to naïve Naïve as dotted line Baranski, G. et al. J Surg Res (2011) Baranski, G. et al. J Bone Marrow Res (2013) 3 hours 7 days

Unit Name Optional Presentation Title Chronic Stress

Unit Name Optional Presentation Title The Addition of CS Prolongs BM Dysfunction *p<0.05 compared to naïve Naïve as dotted line

Unit Name Optional Presentation Title MSCs are Multipotent Cells with Therapeutic Potential Dimmeler S, Losordo D. Stem Cells Review Series: An Introduction. Circ Res 2011.

Unit Name Optional Presentation Title Hypothesis The addition of MSCs to an animal model of acute traumatic injury with hemorrhagic shock followed by chronic restraint stress can protect the bone marrow against post-traumatic dysfunction

Experimental Design MAP 30-35mmHg x 45 min 2hr/day x 6 days

Unit Name Optional Presentation Title Experiment 1 Will MSCs protect the bone marrow against abnormal HPC differentiation?

Unit Name Optional Presentation Title Treatment with MSCs Restores BM Cellularity to Naïve N=6/group; *p<0.05 vs Naïve; ** p<0.05 vs LCHS/CS; dotted line represents naïve

Unit Name Optional Presentation Title MSC Treatment Restores HPC Colony Growth to Naive N=6/group; *p<0.05 vs Naïve; ** p<0.05 vs LCHS/CS; dotted line represents naïve

Unit Name Optional Presentation Title Experiment 2 Can treatment with MSCs prevent prolonged mobilization of HPCs to the peripheral blood?

Unit Name Optional Presentation Title HPC Mobilization

Unit Name Optional Presentation Title Severe Injury Induces a Sustained G-CSF Elevation in Trauma Patients Cook et al. J Am Coll Surg 2013 *p<0.05 compared to control

Unit Name Optional Presentation Title MSCs Reduce Mobilization of HPCs at 7 Days N=6/group; *p<0.05 vs Naïve; ** p<0.05 vs LCHS/CS; dotted line represents naïve

Unit Name Optional Presentation Title MSCs Decrease Plasma G-CSF Levels N=6/group; *p<0.05 vs Naïve; ** p<0.05 vs LCHS/CS; dotted line represents naïve

Unit Name Optional Presentation Title Experiment 3 Can treatment with MSCs prevent the post-injury anemia seen in animals undergoing combined lung contusion, hemmorhagic shock, and chronic stress?

Unit Name Optional Presentation Title MSCs Reverse Post-Traumatic Anemia N=6/group; *p<0.05 vs Naïve; ** p<0.05 vs LCHS/CS; dotted line represents naïve

Unit Name Optional Presentation Title Summary Treatment with MSC effectively reverses BM dysfunction –MSCs increase HPC colony growth to naive levels –MSCs decrease peripheral HPCs with an associated decrease in G-CSF –MSCs increase hemoglobin levels, returning them to naive levels

Unit Name Optional Presentation Title Conclusions MSCs potentially provide a novel therapeutic avenue for prevention of injury-associated anemia Further study into both dosing/timing of administration as well as delineation of immunomodulatory actions of MSCs is warranted

Unit Name Optional Presentation Title Acknowledgements  Letitia Bible, MD  Kim Song, MD  David Livingston, MD  Alicia Mohr, MD  Ziad Sifri, MD Supported by: National Institutes of Health T32 NIH GM A2