Systematic evaluation and network meta-analysis of different cell therapies in the treatment of critical limb ischemia / 中国药房

ABSTRACT

OBJECTIVE To systematically evaluate the efficacy and safety of the four most common cell therapies， namely purified CD34+ （PCCs）， bone marrow mononuclear cells （BMMNCs）， bone marrow mesenchymal stem cells （BMMSCs） and peripheral blood mononuclear cells （PBMNCs） in the treatment of critical limb ischemia （CLI）. METHODS PubMed， Scopus， Embase， Cochrane Central Register of Controlled Trials （CENTRAL） and Web of Science databases were searched from the establishment of each database to June 2023 to collect randomized controlled trials （RCTs） comparing the efficacy and safety of four different cell therapies， namely PCCs， BMMNCs， BMMSCs and PBMNCs， with other cell therapies or standard therapy （ST） in the treatment of CLI. The outcomes indexes included amputation rate， ankle-brachial index （ABI）， transcutaneous oxygen partial pressure （TCPO2）， ulcer healing rate， pain-free walking distance （PFWD） and angiogenesis. After data extraction from clinical studies that met the inclusion criteria， the RoB 2.0 tool was used to assess the risk of bias， and Stata 15.0 software was used for statistical analysis. RESULTS Meta-analysis included 22 studies， involving 1 318 patients. The treatment groups involved 4 types of cell therapies， namely PCCs，BMMNCs， BMMSCs， and PBMNCs. Network meta-analysis showed that the amputation rates of the four cell therapies groups were lower than that of ST group， and only the difference in PBMNCs group was statistically significant（P＜0.05）. Four cell interventions were better than ST in improving ABI （P＜0.05）， and BMMNCs had the most significant effect on improving ABI. PBMNCs and BMMNCs groups had statistically significant differences in improving TCPO2， compared with ST group and BMMSCs group （P＜0.05）. Four cell interventions were better than ST in improving ulcer healing rate， among which BMMNCs group had no statistical difference with ST group （P＞0.05）； ulcer healing rates of the other three groups were higher than that of ST group （P＜0.05）， and those of PBMNCs and BMMSCs groups were significantly higher than that of BMMNCs group （P＜ 0.05）. BMMSCs group had a significantly better effect on improving the PFWD of patients than the ST group after transplantation， with statistical significance （P＜0.05）， but there was no significant difference in PBMNCs and BMMNCs groups compared with ST group （P＞0.05）. The three cell therapies of BMMSCs， BMMNCs and PBMNCs had a significantly better effect on angiogenesis than the ST group， and the BMMSCs group had a significantly better effect than the BMMNCs and PBMNCs groups， with statistical significance （P＜0.05）. CONCLUSIONS The four cell therapies can improve the prognosis of CLI patients to varying degrees. PBMNCs show the lowest amputation rate after transplantation and have the most significant effect on improving TCPO2 and improving the ulcer healing rate. BMMNCs possess the most significant effect on improving ABI. BMMSCs represent obvious advantages in PFWD and angiogenesis.