Impact of sepsis on bone marrow mesenchymal stem cells and its implications for hematopoiesis and immunosuppression.

Objective and design: Septic patients often exhibit disruption of the normal hematopoiesis, leading to hematological abnormalities such as anaemia, leukopenia, and thrombocytopenia. We hypothesized that sepsis-induced changes in bone marrow mesenchymal stromal cells (BM-MSCs) contribute to the abnormal hematopoiesis observed in these patients.

Material and methods: We established lineages of BM-MSCs from male BALB/c mice collected 8 h after the sham (MSC-CT) or cecal ligation and puncture surgery (MSC-Sepsis). We evaluated BM-MSCs proliferation, plasticity, and immunomodulatory properties.

Results: No differences in multipotency or immunophenotypic profiles were detected between the MSC-CT and MSC-Sepsis groups. However, MSC plasticity was clearly affected by sepsis, as osteoblast differentiation was impaired in MSC-Sepsis. Since differentiation capacity is closed linked to mitochondrial dynamics and function, we assessed mitochondrial health and found that MSC-Sepsis presented depolarized mitochondria. The photoelectron micrographs supported these findings, as MSC-Sepsis presented higher number of small mitochondria around the nuclei and deformed cristae in the mitochondria. Additionally, cytokine array analysis revealed a marked reduction in the expression of several cytokines and chemokines in MSC-Sepsis.

Conclusion: Our findings demonstrate that sepsis induces several functional alterations in MSC that may impair bone marrow homeostasis and contribute to both the acute immune response and long-term complications in sepsis survivors.