Mesenchymal Stem Cells Reverse Anemia and Bone Marrow Dysfunction Following Trauma, Hemorrhagic Shock, and Chronic Stress
Author(s):
Amy Gore; Letitia Bible, Rutgers-NJMS; David Livingston, New Jersey Medical School; Alicia Mohr, University of Florida; Ziad Sifri, UMDNJ-NJ Medical School
Background: Animals undergoing lung contusion (LC) followed by hemorrhagic shock (HS) and daily chronic stress (CS) exhibit persistent bone marrow (BM) dysfunction and anemia lasting up to seven days following injury.
Hypothesis: Given the protective immunomodulatory effects of Mesenchymal stem cells (MSCs), we hypothesize that MSCs can attenuate BM dysfunction and anemia following LCHS/CS.
Methods: Male Sprague-Dawley rats (n=6/group) were subjected to LCHS/CS ± single IV dose of 5 x 106 allogeneic MSC. Animals underwent two hours of daily restraint stress until sacrifice (day7). BM cellularity and growth of hematopoietic progenitor cell (HPC) colonies (CFU-E, BFU-E, and CFU-GEMM) were analyzed. Peripheral blood (PB) was collected for hemoglobin analysis, flow cytometry for HPCs, and plasma G-CSF level by ELISA. Data was analyzed by one-way ANOVA followed by Tukey’s Multiple Comparison Test.
Results: Treatment with MSCs post LCHS/CS resulted in a 31% increase in BM cellularity as compared to LCHS/CS alone. Similarly, there were 53, 63, and 59% increases in CFU-E, BFU-E, and CFU-GEMM respectively. This was associated with an increase in hemoglobin by 27%. Furthermore, MSC administration resulted in a 77% decrease in the number of HPCs mobilized to the periphery and 132% decrease in plasma G-CSF level.
Conclusions: The administration of a single dose of MSCs post injury reverses the persistent anemia, HPC mobilization, G-CSF elevation, and bone marrow dysfunction seen one week following LCHS/CS. Further study into the immunomodulatory effects of MSCs following trauma, shock and chronic stress is warranted.