fig3

Figure 3. The breaking of the vicious cycle in hyperinflammatory conditions by bone marrow-derived naive stem cells. Necrosis in the target tissues initiate an M1 macrophage/microglia-induced cytokine cascade and activation of other cell types resulting in cell proliferation, further pro-inflammatory cytokine release (mainly IL-6), and propagation of tissue damage. In case of an imbalanced release of pro- and anti-inflammatory cytokines, phagocytosis of the apoptotic vesicles is blocked, and a vicious cycle will follow by the non-phagocytized vesicles, becoming necrotic. Intravenous (IV) and/or intrathecal (ITh) transplantation of stem cells then may restore the imbalanced cytokine levels and break the vicious cycle by polarization of cytotoxic M1 into antagonizing M2 immune cells on the one, and inhibition of the up‐regulation of the protein expression of inflammatory markers (GSK-3β) on the other hand.