Fig. 2.
Impact of mesenchymal stem cells on ischemia–reperfusion injury pathways. Ischemia is a significant cause of acute organ injury that results from a decrease in regional oxygen delivery (such as low blood flow or hypoxemia), leading to inefficient anaerobic glycolysis as the major source of ATP production and ATP deficit. However, much of the tissue damage occurs during the reperfusion phase, leading to mitochondrial permeability transition pore opening, proglycolytic enzyme depletion, proapoptotic proteome shift and mitochondrial dysfunction inducing oxidative stress. MSC can decrease ischemia–reperfusion induced injury by: (1) restoring ATP levels by possibly mitochondrial transfer through connexin-43 channels and replenishing depleted glycolytic enzymes; (2) decreasing reactive oxygen species/reactive nitrogen species generated during oxidative stress by either preventing their release, circumventing the depletion of key enzymes or by transferring reactive oxygen species scavengers (such as peroxiredoxins and glutathione S-transferase) into injured cells; and (3) restoring proteomic alterations by activating prosurvival phosphatidylinositide 3-kinases/protein kinase B pathway via cluster of differentiation 73 or inhibiting p38 MAPK-caspase 3 pathway. ATP = adenosine triphosphate; CD73 = cluster of differentiation 73; MAPK = mitogen-activated protein kinases; MSC = mesenchymal stem cell; OS = oxidative stress; PI3/Akt = phosphatidylinositide 3-kinases/protein kinase B; PTP = permeability transition pore; RNS = reactive nitrogen species; ROS = reactive oxygen species; TCA = tricarboxylic acid cycle.