Mesenchymal Stem Cells Reverse Anemia and Bone Marrow
Mesenchymal Stem Cells Reverse Anemia and Bone Marrow Dysfunction Following Trauma, Shock, and Chronic Stress Amy Gore, MD, PGY 4 Nothing to Disclose Department of Surgery, Division of Trauma Rutgers, The State University of New Jersey, Newark, NJ
ROLE OF BONE MARROW AFTER INJURY ABNORMAL HPC DIFFERENTIATION Within the BM EXCESSIVE HPC MOBILIZATION Loss of cells from BM Injuryassociated anemia Impaired wound healing
Optional Presentation Title Bone Marrow Dysfunction Following Acute Injury and Hemorrhagic Shock 3 hours Baranski, G. et al. J Surg Res (2011) Baranski, G. et al. J Bone Marrow Res (2013) Unit Name 7 days *p<0. 05 compared to naïve Naïve as dotted line
Optional Presentation Title HPC Mobilization Following Trauma and Shock 3 hours Baranski, G. et al. J Surg Res (2011) Baranski, G. et Unit Name al. J Bone Marrow Res (2013) 7 days *p<0. 05 compared to naïve Naïve as dotted line
Optional Presentation Title Chronic Stress Unit Name
Optional Presentation Title The Addition of CS Prolongs BM Dysfunction Unit Name *p<0. 05 compared to naïve Naïve as dotted line
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 Unit Name
Experimental Design 2 hr/day x 6 days MAP 30 -35 mm. Hg x 45 min
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 Unit Name N=6/group; *p<0. 05 vs Naïve; ** p<0. 05 vs LCHS/CS; dotted line represents naïve
Optional Presentation Title MSC Treatment Restores HPC Colony Growth to Naive Unit Name N=6/group; *p<0. 05 vs Naïve; ** p<0. 05 vs LCHS/CS; dotted line represents naïve
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 Unit Name Cook et al. J Am Coll Surg 2013 *p<0. 05 compared to control
Optional Presentation Title MSCs Reduce Mobilization of HPCs at 7 Days Unit Name N=6/group; *p<0. 05 vs Naïve; ** p<0. 05 vs LCHS/CS; dotted line represents naïve
Optional Presentation Title MSCs Decrease Plasma G-CSF Levels Unit Name N=6/group; *p<0. 05 vs Naïve; ** p<0. 05 vs LCHS/CS; dotted line represents naïve
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 Unit Name N=6/group; *p<0. 05 vs Naïve; ** p<0. 05 vs LCHS/CS; dotted line represents naïve
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 T 32 NIH GM 069330 -06 A 2 Unit Name
- Slides: 23