Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Diabetic Foot Ulcers and Peripheral Artery Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Growing evidence has supported the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot and lower extremity peripheral artery disease (PAD), but their results are not consistent. Thus, the authors conducted the first meta-analysis concerning the safety and efficacy of UCMSC treatment in diabetic foot patients. 8 English and Chinese databases were searched to identify randomized controlled trials regarding UCMSC therapy in diabetic foot patients. Two independent investigators carried out literature inclusion, data extraction, and quality assessment. Meta-analysis was performed using ReviewManager 5.4.1., 6 RCT studies involving 380 patients were included. Primary endpoints included ulcer healing, transcutaneous oxygen pressure (TcPO₂), ankle-brachial index (ABI), and intermittent claudication. Compared with conventional treatment, patients who accepted UCMSC therapy had a better ulcer healing rate (Odds Ratio (OR) = 2.88 [1.20–6.91]), TcPO₂ (standardized mean difference (SMD) = 1.39, [0.01–2.77]), and ABI improvement (SMD=1.22 [0.30–2.13]). Moreover, they also experienced significantly better improvements in pain amelioration, skin temperature, and ulcer area reduction. Whereas, intermittent claudication cannot be ameliorated by UCMSC therapy (SMD=0.83 [-0.45–2.10]). Additionally, neovascularization, examined by angiography, was significantly promoted after UCMSC administration. Moreover, two studies recorded adverse events during follow-up, which were considered to be transient, minor, and regional. The present meta-analysis validated that UCMSC treatment enhances diabetic foot ulcer healing and circulation recovery, and has a promising safety profile, though limited by incomplete reporting. Larger-sample multicenter randomized controlled trials and longer-term follow-up are urgently needed to further explore the safety and efficacy of UCMSC treatment in diabetic foot patients. The meta-analysis was prospectively registered on PROSPERO.