Mesenchymal stem cells reverse bone marrow dysfunction following injury and stress

BACKGROUND Bone marrow (BM) dysfunction following experimental lung contusion (LC) resolves in 7 days; however, if followed by chronic stress (CS) following, BM dysfunction is persistent. Mesenchymal stem cells (MSCs) have protective immunomodulatory effects. We hypothesize that MSC can protect the BM against the deleterious effect of CS following LC. METHODS Male Sprague-Dawley rats (n = 6-7 per group) underwent LC or LC/CS MSC injection. CS consisted of a daily 2-hour period of restraint with repositioning and alarming every 30 minutes to prevent habituation. A single intravenous dose of 5 x 10(6) MSCs was given within 10 minutes following LC. Animals were sacrificed at Day 7, and peripheral blood (PB) and BM were collected. Flow cytometry was used to assess hematopoietic progenitor cells (HPCs) mobilized to PB. Plasma granulocyte colony-stimulating factor (G-CSF) levels were measured by enzyme-linked immunosorbent assay. BM cellularity and growth of BM HPC colonies (colony-forming unit-erythroid [CFU-E], burst-forming unit-erythroid [BFU-E], colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte [CFU-GEMM]) were also evaluated. RESULTS As previously reported, the addition of CS to LC resulted in a 32% decrease in BM cellularity; significant decreases in CFU-GEMM, BFU-E, and CFU-E; and marked increase in HPC in the PB as compared with the naive animals. The addition of MSC to LC/CS resulted in a 22% increase in BM cellularity and significant increases in CFU-GEMM, BFU-E, and CFU-E cultured from the BM. MSCs additionally reduced plasma G-CSF, prevented prolonged mobilization of HPC to PB, and restored colony growth to naive levels. CONCLUSION CS following LC results in persistent BM dysfunction manifested by a significant decrease in cellularity, HPC colony growth, and increased G-CSF levels and HPC mobilization to the PB at 7 days following injury. The addition of a single dose of MSCs following acute traumatic injury reverses the deleterious effects of CS on BM function. Further study is warranted to better understand the mechanisms behind MSC-mediated protection of BM function in the setting of CS.