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

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.

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.

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.

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.