Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study

Abstract

Abstract Background: Mesenchymal stem cell (MSC) based therapy holds great promise for cell-based therapy in regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. Methods: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events (SAEs) and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. Results: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p=0.042). EQ-VAS scores improved significantly at 2 month (p=0.023) and continued until the end of the 6-month visit (p=0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p＜0.05). MSC transplantation improved the function of four-meter walking test (4MWT) compared with the placebo group with a decrease of 2.05s at 6 months of follow-up (p=0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p=0.002). Inflammatory cytokines (TNF-a, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p=0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. Conclusion: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance and reducing chronic inflammation, suggest HUC-MSC therapy may be a promising potential treatment option for aging frailty. Trial Registration: Clinicaltrial.gov; NCT04314011; Registered 10 December, 2019; URL: https://clinicaltrials.gov/ct2/show/NCT04314011.