Mitochondria derived from Stem cells modulated the biological behavior of monocyte-macrophages and inhibited inflammatory bone resorption.

Abstract

Background: The transfer of mitochondria from stem cells effectively attenuates the viability of inflammatory cells. However, there is a paucity of research supporting the inhibitory effect of stem cells on inflammatory bone resorption through mitochondrial transfer.

Methods: Mouse bone resorption models were established to investigate the impact of stem cell-derived mitochondria. Stem cells, stem cell-derived mitochondria and exosomes were injected into the animal models for experimental research. Healthy mice and mice with bone resorption were included as the control groups. The mitochondrial transfer and bone resorption of mice calvaria were evaluated by immunofluorescence, gross morphology, micro-computed tomography (micro-CT), immunohistochemical staining. Monocyte-macrophages were incubated with stem cell-derived mitochondria as experimental group. Monocyte-macrophages and activated monocyte-macrophages cultured separately served as the control groups. The mitochondrial transfer and biological behavior of monocyte-macrophages were evaluated by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Multiskan FC, and histochemical staining.

Results: Stem cell-derived mitochondria were successfully transferred to monocyte-macrophages. In vivo, local injection of stem cells, mitochondria, and exosomes effectively mitigated inflammatory cell infiltration, suppressed osteoclast maturation, and demonstrated a higher relative bone volume in mouse bone resorption models compared to the negative control group. In vitro, the co-incubation of mitochondria effectively suppressed the secretion of inflammatory cytokines, proliferation, fusion, and osteoclastogenesis in monocyte-macrophages compared to the control groups.

Conclusions: The modulation of monocyte-macrophages biological behaviors by stem cells may occur through the transfer of mitochondria, thereby mitigating inflammatory bone resorption.