Laromestrocel, an allogeneic mesenchymal stem cell therapy, produced clinically meaningful improvements in physical function among 148 frail older adults. The treatment increased 6-minute walk test distance by 63.4 meters at 9 months compared to placebo, with effects showing clear dose-dependency. The therapy also decreased soluble TIE2 receptor levels, suggesting improved vascular function as a potential mechanism. This represents the first successful randomized trial demonstrating that stem cell therapy can meaningfully reverse functional decline in human frailty. The 63-meter improvement exceeds the minimal clinically important difference for the 6-minute walk test, indicating real-world benefit for patients. However, the effect size diminished at 6 months, raising questions about treatment durability and optimal dosing schedules. The trial's moderate size and ambulatory population limit generalizability to more severely frail individuals. While promising, this single study requires replication before clinical adoption. The identification of TIE2 as a biomarker could enable personalized treatment approaches, potentially transforming how we address age-related functional decline.