Fig. 2

Preconditioning strategies to improve MSC survival. a Hypoxic preconditioning promotes stabilization of hypoxia-inducible factor 1-α (HIF-1α), which decreases reactive oxygen species (ROS) levels in MSC mitochondria, activating nuclear factor kappa B (NFκB). HIF-1α also stimulates synthesis of normal cellular prion protein (PrPC). NFκB and PrPC promote expression of anti-apoptotic proteins, repairing growth factors, and antioxidant enzymes. b Oxidative preconditioning raises ROS levels in MSC mitochondria, activating extracellular signal-regulated kinases (ERK), leading to expression of genes involved with survival. c Heat shock preconditioning leads MSCs to produce heat shock proteins (HSPs), which promote survival and potentiation through three different signaling pathways: ERK, PI3K/AKT, and NFκB. d Nutrient-depletion preconditioning inhibits mammalian target of rapamycin complex-1 (mTORC1), interrupting protein, lipid, and nucleotide synthesis. On the other hand, inhibition of mTORC1 favors the activity of proteins such as transcription factor EB (TFEB), which promotes expression of genes related to lysosomal biogenesis and leads to protective autophagic processes