O26 – Mesenchymal Stem Cells Reverse Chronic Stress Induced Bone Marrow Dysfunction Following Traumatic Injury
Author(s):
Background: Bone marrow (BM) dysfunction following lung contusion (LC) resolves quickly, but the addition of chronic stress (CS) to LC results in persistent bone marrow dysfunction. Mesenchymal stem cells (MSC) have protective immunomodulatory effects which have not been tested in the setting of CS.
Hypothesis: We hypothesize that MSC can protect the BM against the deleterious effect of CS following LC.
Methods: Male Sprague-Dawley rats (n=6-8/group) underwent LC or LC/CS ± MSC injection. CS consisted of a daily 2 hour period of restraint with repositioning and exposure to alarms every 30 minutes to prevent habituation. A single iv dose of 5 x 106 MSC in 1mL IMDM media was given ten minutes following LC. Animals were sacrificed at day seven and peripheral blood (PB) and BM were collected. Flow cytometry was used to assess HPCs mobilized to PB. BM cellularity and growth of BM HPC colonies (CFU-E, BFU-E, CFU-GEMM) were evaluated.
Results: The addition of CS to LC resulted in a 32% decrease in BM cellularity, a significant decrease in CFU-GEMM, BFU-E, and CFU-E and marked increase in HPC in the PB as compared naïve animals. The addition of MSC to LC/CS resulted in a 22% increase in BM cellularity and significant increase in CFU-GEMM, BFU-E, and CFU-E cultured from the BM. The addition of MSC to LC/CS prevented prolonged mobilization of HPC to PB and restored colony growth to naïve levels.
Conclusions: Chronic stress following LC results in persistent BM dysfunction manifested by a significant decrease in cellularity, HPC colony growth and increased HPC mobilization to the PB at seven days following injury. The addition of MSC following an acute traumatic injury reversed the deleterious effects of CS on BM function. Further study into the immunomodulatary effects of MSC in the setting of CS setting is warranted.