Prospective Application of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Disseminated Intravascular Coagulation

Abstract

Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management.

Keywords: anticoagulant therapy; disseminated intravascular coagulation; macrophage polarization; mesenchymal stem cell-derived exosomes; neutrophil extracellular traps.

Graphical abstract

Figure 1

Schematic diagram of NET-induced DIC. NETs stimulate endothelial cells to release TF and activate platelet TLR4, leading to increased vWF and D-dimer levels. Consequently, fibrinogen-to-fibrin conversion, Factor XII activation, and the coagulation cascade are triggered, while tPA is inhibited and TFPI is degraded, resulting in thrombosis and DIC onset.

Figure 2

Mesenchymal stem cell-derived exosomes (MSC-Exos) regulate M1/M2 macrophages to alleviate inflammatory cytokine storms. Upon cytokine and LPS stimulation, monocytes mainly differentiate into M1 and M2 macrophages. M1 macrophages secrete tumour necrosis factor-α, interleukin (IL)-6, and other pro-inflammatory cytokines, and induce inflammatory cytokine storms. To alleviate inflammatory damage, M2 macrophages play an anti-inflammatory role by secreting IL-10, transforming growth factor-β, and other anti-inflammatory cytokines. MSC-Exos can inhibit M1-type macrophages, promote M2-type macrophages, restore balance to the polarization of M1/M2 macrophages, and exert anti-inflammatory repair functions, with the potential to alleviate DIC.

Figure 3

Schematic diagram of the role of MSC-Exos in Nrf2 pathway activation and NF-κB pathway inhibition. MSC-Exos mitigate inflammation and the coagulation cascade through activation of the Nrf2 pathway and inhibition of the NF-κB pathway.