Journal Article

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

Zhai, Miaomiao, Li, Qingqing, Jia, Wenwen, Ye, Tong, Ge, Jianli, Liu, Hailiang, Jiang, Hua, Geng, ShaSha, Chen, Xin, Zhao, Zhengmei, Zhu, Yingqian, Sun, Keping, Liu, Zhongmin, Li, Yan, Huang, Ce, Yuan, Huixiao, Li, Yang, Zheng, Liang

2024

Overview

Background Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of 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 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 of MSCs group 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 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s 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-α, 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 that HUC-MSC therapy may be a promising potential treatment option for aging frailty. Trial Registration : Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aged / Aged patients / Aged, 80 and over / Aging - physiology / Aging frailty / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Care and treatment / Cell Biology / Chronic inflammation / Clinical trials / Double-Blind Method / Female / Frailty - therapy / Health aspects / Human umbilical cord derived mesenchymal stem cells / Humans / Life Sciences / Male / Mesenchymal Stem Cell Transplantation - adverse effects / Mesenchymal Stem Cell Transplantation - methods / Mesenchymal Stem Cells - cytology / Middle Aged / Quality of Life / Quality of life, physical performance / Randomized controlled trial / Regenerative Medicine/Tissue Engineering / Safety and efficacy / Stem Cells / Transplantation / Treatment Outcome / Type 2 diabetes / Umbilical Cord - cytology