Fig. 4: Strategies targeting innate immunity.

In CRT, the standard procedure involves the injection of cells into the brain using a needle, which induces needle trauma and subsequent secretion of various innate immune response factors, including DAMPs, pro-/anti-inflammatory cytokines, and chemokines. These factors activate surrounding glial cells and lead to the infiltration of peripheral immune cells into the brain, contributing positively to damage repair. However, they also exert a detrimental effect on grafted cells, resulting in severe cell death of mDANs. A potential strategy to enhance the survival of grafted cells involves obtaining autologous T_REG cells from the patient, increasing their quantity and functionality, and confirming improved therapeutic effects through co-transplantation into the brain. Additionally, exploring the efficacy of inhibitors, neutralizing antibodies, and encapsulation methods to enhance the survival of grafted cells within the inflammatory microenvironment, combined with the application of T_REG technology, represents a promising direction for future advancements in CRT.