Mesenchymal stem cells reverse trauma and hemorrhagic shock-induced bone marrow dysfunction

• Published in: The Journal of surgical research 2015-12, Vol.199 (2), p.615-621
• Main Authors: Gore, Amy V., MD, Bible, Letitia E., MD, Livingston, David H., MD, Mohr, Alicia M., MD, Sifri, Ziad C., MD
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - complications; Animals; Bone Marrow Diseases - blood; Bone Marrow Diseases - etiology; Bone Marrow Diseases - therapy; G-CSF; Granulocyte Colony-Stimulating Factor - blood; Hematopoietic progenitor cells; Hematopoietic Stem Cells - physiology; Hemorrhagic shock; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic - complications; Surgery; Trauma
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2015.06.023

Abstract Background Lung contusion (LC) followed by hemorrhagic shock (HS) causes persistent bone marrow (BM) dysfunction lasting up to 7 d after injury. Mesenchymal stem cells (MSCs) are multipotent cells that can hasten healing and exert protective immunomodulatory effects. We hypothesize that MSCs can attenuate BM dysfunction after combined LCHS. Materials and methods Male Sprague–Dawley rats ( n  = 5–6 per group) underwent LC plus 45 min of HS (mean arterial pressure of 30–35). Allogeneic MSCs (5 × 106 cells) were injected intravenously after resuscitation. At 7 d, BM was analyzed for cellularity and growth of hematopoietic progenitor cell (HPC) colonies (colony-forming unit–erythroid; burst-forming unit–erythroid; and colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte). Flow cytometry measured %HPCs in peripheral blood; plasma granulocyte colony-stimulating factor (G-CSF) levels were measured via enzyme-linked immunosorbent assay. Data were analyzed by one-way analysis of variance followed by the Tukey multiple comparison test. Results As previously shown, at 7 d, LCHS resulted in 22%, 30%, and 24% decreases in colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte, burst-forming unit–erythroid, and colony-forming unit–erythroid colony growth, respectively, versus naive. Treatment with MSCs returned all BM parameters to naive levels. There was no difference in %HPCs in peripheral blood between groups; however, G-CSF remained increased up to 7 d after LCHS. MSCs returned G-CSF to naive levels. Plasma from animals receiving MSCs was not suppressive to the BM. Conclusions One week after injury, the persistent BM dysfunction observed in animals undergoing LCHS is reversed by treatment with MSCs with an associated return of plasma G-CSF levels to normal. Plasma from animals undergoing LCHS plus MSCs was not suppressive to BM cells in vitro. Treatment with MSCs after injury and shock reverses BM suppression and returns plasma G-CSF levels to normal.