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

Figure 5 Specific pre-strategies and their key molecule targets for enhancing stem cell transplantation therapy. These pre-strategies mainly include preconditioning (e.g., exposure to oxidative stress, heat shock, and ischemic/hypoxic injury), pretreatment (e.g., drug treatment, cytokines, antioxidants, nitric oxide, glucose deprivation, growth factors, miRNAs, and exosomes), genetic strategies (e.g., AAV vector mediated transfection, Liposome-based transfection, and CRISPR/Cas9-based genome editing), and other methods (e.g., 3D culture technologies, co-transplantation, and nanotechnology). The core ideas of these pre-strategies are to upregulate the survival factors (e.g., Bcl-2, Akt, SMAC, mTOR, SOD2, STAT3, HSC 70, ERK, and Nrf2) and downregulate the death catalyzers (e.g., caspase, p53, TNFa, Bax, Cyt c, XIAP, MAPK, and Atg). However, there are few methods targeting all of these molecules at the same time during the co-network. Also, studies pay more attention to certain signaling such as Bcl-2 and mTOR, and other signals such as Atg or XIAP still need further mining.