Modulation of Stem Cell Survival and Engraftment: Implications for Stem Cell-Based Therapy

Stem cell transplantation holds promise for the treatment of degenerative diseases, tissue injuries, and malignancies. Despite this potential, clinical outcomes have often fallen short, largely due to limited survival and engraftment of transplanted cells at target sites. Recent research efforts have focused on optimizing cell-based therapies through improved understanding of stem cell biology and responsiveness to environmental cues. Emerging evidence indicates that the hostile post-transplantation microenvironment contributes to irreversible cellular damage and death, driven by metabolic dysfunction, immune-mediated responses, reactive oxygen species (ROS), altered biomechanical rigidity, and disrupted intercellular communication. To address these challenges, various strategies have been explored, including supplementation with exogenous metabolic substrates, enhancement of vascular remodeling, administration of antioxidants, and the application of three-dimensional (3D) stem cell spheroids. This review synthesizes current approaches aimed at improving cell viability and therapeutic efficacy in regenerative medicine.