Mitochondrial transplantation as an immunomodulatory strategy: Modulating polymorphonuclear leukocytes for functional...

Following biomaterial implantation, modulation of the acute immune response is essential for tissue regeneration. Polymorphonuclear leukocytes (PMNs) are critical effector cells in wound healing, and PMN dysfunction is mediated by mitochondrial dysfunction and can lead to prolonged inflammation and tissue damage. It was hypothesized that mitochondrial transplantation could be applied to PMNs in pro-inflammatory states as a means of upregulating regenerative proteins. Primary human PMNs were isolated from donor blood. Isolated PMNs and exogenous mitochondria were co-incubated to induce mitochondrial transplantation. Resulting interactions were assessed through microscopy to confirm initial uptake and mitochondria membrane potential retention, intracellular reactive oxygen species (ROS) analyses (n = 5), and PMN secretome quantification (n = 10) using multiplex protein analysis. Human PMNs were able to successfully uptake delivered mitochondria, and regenerative factors essential for tissue repair and immune cell recruitment including fibroblast growth factor-2 (FGF-2), interleukin (IL)-22, monocyte chemoattractant protein-1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF) were significantly upregulated, indicating that exogenous mitochondria represent promising modulators of PMN function with broad clinical potential.