Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications

Figure 2 Mechanisms of extrinsic apoptotic pathways in stem cells. The extrinsic apoptotic pathway (also known as the death receptor-dependent pathway) is induced by the connection between death receptors exposed on the cell surface [tumor necrosis factor (TNF) receptor] and the specific TNF family ligands. Subsequently, this signaling causes a conformational change leading to the recruitment of Fas-associated death domain (FADD) and allows interactions between FADD and casp-8 and/or the casp-10, resulting in the cleavage and activation of casp-3 and casp-7 through their death domain. Finally, the active and cleaved casp-3 induces changes in phosphatidylserine exposure, DNA fragmentation, and the formation of apoptotic bodies. Also, casp-8 can target the BH3-only protein Bid and cleave Bid to a truncated fragment t-Bid, which could connect to the extrinsic apoptotic pathways. The T-shaped lines indicate inhibitory interactions involved in this pathway, while the solid arrows indicate activating interactions. FADD: Fas-associated death domain.