Dear editor, Ischemic stroke, a well-known age-related disorder (Cai et al., 2022b), resulting from the occlusion of cerebral blood vessels and the ensuing neuronal damage, has emerged as a leading cause of mortality and disability worldwide (Zhang and Chopp, 2009). It represents a significant global health challenge. The pursuit of innovative treatment strategies for ischemic stroke has become an urgent scientific priority. Stem cell therapy has gained prominence as a promising therapeutic modality for attenuating ischemic brain injury and facilitating repair in affected region (Zhu et al., 2023). Among these, mesenchymal stem cells (MSCs) have garnered particular attention for their potential in ischemic stroke therapy, attributed to their capacity to secrete therapeutic biomolecules that provide neuroprotection, stimulate angiogenesis, and modulate immune responses (Stonesifer et al., 2017). Despite their promise, a multitude of challenges impede the realization of MSCs’ therapeutic potential. For instance, the variability and heterogeneity of MSCs restricts the number of cells available for transplantation. Additionally, as the number of passages increases, MSCs exhibit increased cellular senescence and a diminished capacity for differentiation. Moreover, the harsh microenvironment within the recipient ischemic tissue often leads to inadequate retention and survival of transplanted cells at the target site (Stonesifer et al., 2017; Cai et al., 2022a). Consequently, developing strategies to provide superior cell materials is essential for enhancing the therapeutic efficacy of MSC-based treatments. Recent studies have shown that targeted gene editing in stem cells can boost their functionality, leading to improved posttransplant survival and therapeutic benefits (Cai et al., 2022a). Our previous studies have highlighted that activating FOXO3, a gene linked to longevity, in MSCs derived from human embryonic stem cells (hESCs) reduces cellular senescence, boosts self-renewal, and strengthens stress resistance (Yan et al., 2019; Lei et al., 2021).