Synergistic mesenchymal and neural stem cell therapy: Advancing neurorestoration in cerebral infarction

Recent clinical and translational studies have increasingly highlighted the promise of combined stem cell strategies for neurorestoration following ischemic stroke. In this correspondence, we reflect on the recent trial by Yang et al, which reported that co-transplantation of mesenchymal stem cells (MSCs) and neural stem cells (NSCs) yielded significantly greater functional recovery in patients with acute cerebral infarction, as evidenced by improvements in both Barthel Index and National Institutes of Health Stroke Scale scores. Notably, this dual-cell intervention was accompanied by robust elevation of angiogenic and neurotrophic mediators, particularly vascular endothelial growth factor and basic fibroblast growth factor, suggesting a biologically plausible mechanism for the observed clinical benefit. MSCs contribute through trophic support, immunomodulatory effects, and promotion of vascular regeneration, whereas NSCs primarily facilitate neuronal replacement and reorganization of neural circuits. Together, these mechanisms offer a comprehensive, multitargeted approach to address the multifactorial nature of stroke pathology. Building on this pivotal work, we call for mechanistic studies and multicenter randomized clinical trials to refine cell dosing, timing, and bioengineering strategies, paving the way for the clinical integration of MSC/NSC co-therapy as a next-generation regenerative treatment for stroke.