Mesenchymal stem cells in treatment of arteriosclerosis obliterans of lower extremities: systematic review and meta-analysis

doi:10.12307/2026.597

Abstract

Abstract: OBJECTIVE: To systematically evaluate the clinical efficacy of mesenchymal stem cell therapy for the treatment of arteriosclerosis obliterans of lower extremities.
METHODS: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, Cochrane Library, Scopus, Google Scholar, CNKI, WanFang Data, VIP, and CBM for randomized controlled trials on the use of mesenchymal stem cells in the treatment of arteriosclerosis obliterans of lower extremities. The search covered the period from the inception of each database until July 2024. Relevant studies were screened and data were extracted based on predefined inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software, including amputation rate, amputation-free survival rate, ulcer healing rate, ankle-brachial index, transcutaneous oxygen pressure, and pain-free walking distance.
RESULTS: A total of nine randomized controlled trials were included in the meta-analysis. The meta-analysis results showed that compared with the control group, patients in the mesenchymal stem cell treatment group had significant improvements in amputation-free survival rate [RR=1.23, 95%CI(1.07, 1.42), P=0.004], amputation rate [RR=0.55, 95%CI(0.35, 0.85), P=0.007], ulcer healing rate [RR=1.95, 95%CI(1.51, 2.52), P < 0.001], ankle-brachial index [MD=0.16, 95%CI(0.13, 0.19), P < 0.001], transcutaneous oxygen pressure [SMD=1.62, 95%CI(0.87, 2.37), P < 0.001], and pain-free walking distance [MD=131.81, 95%CI(3.56, 260.06), P=0.04]. However, there was no significant difference in mortality [RR=1.13, 95%CI(0.62, 2.06), P=0.68].
CONCLUSION: Mesenchymal stem cell therapy for lower extremity atherosclerotic occlusive disease shows a trend of improvement in some clinical indicators. However, due to the limitations of the included literature, more high-quality, multicenter, and large-sample randomized controlled trials are needed in the future.

Key words: mesenchymal stem cell, atherosclerosis, arteriosclerosis obliterans of lower extremities, ulcer healing, exosome, clinical efficacy, meta-analysis, randomized controlled trial

CLC Number:

Wang Zhenze, Liu Fende, Zhang Rui, Li Wujun. Mesenchymal stem cells in treatment of arteriosclerosis obliterans of lower extremities: systematic review and meta-analysis [J]. Chinese Journal of Tissue Engineering Research, 2026, 30(7): 1869-1876.

Figures/Tables 4

2.4 Meta分析结果 2.4.1 无截肢生存率共有6项研究比较了无截肢生存率[9，11，14-17]，经过异质性检验提示各项研究间不存在异质性(I2=25%，P=0.25)，故采用固定效应模式分析。Meta结果显示，间充质干细胞组与对照组无截肢生存率比较存在统计学差异[RR=1.23，95%CI(1.07，1.42)，P=0.004]，见图4A。 2.4.2 截肢率共有6项研究比较了截肢率[9，11，14-17]，经过异质性检验提示各项研究间不存在异质性(I2=15%，P=0.32)，故采用固定效应模式分析。Meta结果显示，间充质干细胞组与对照组截肢率比较存在统计学差异[RR=0.55，95%CI(0.35，0.85)，P=0.007]，见图4B。 2.4.3 死亡率共有3项研究比较了死亡率[9，11，15]，经过异质性检验提示各项研究间不存在异质性(I2=0%，P=0.56)，故采用固定效应模式分析。Meta结果显示，间充质干细胞组与对照组死亡率比较无统计学意义[RR=0.88，95%CI(0.49，1.60)，P=0.68]，见图4C。 2.4.4 溃疡愈合率共有5项研究比较了溃疡愈合率[11，14-17]，经过异质性检验提示各项研究间存在异质性(I2=70%，P=0.21)且异质性具有统计学差异(P < 0.05)，需要进行异质性查找。对5项研究分别采用逐一剔除的方法进行敏感性分析，发现GUPTA等[15]对异质性影响较大，去掉该研究后再进行异质性分析，结果显示其余文献不存在异质性(I2=0%，P=0.77)，故采用固定效应模式分析。Meta结果显示，间充质干细胞组与对照组溃疡愈合率比较有统计学意义[RR=1.95，95%CI(1.51，2.52)，P < 0.000 1]，见图4D。 2.4.5 踝肱指数共有5项研究比较了踝肱指数[12-14，16-17]，经过异质性检验提示各项研究间不存在异质性(I2=0%，P=0.62)，故采用固定效应模式分析。Meta结果显示，间充质干细胞组与对照组踝肱指数比较存在统计学差异[MD=0.16，95%CI(0.13，0.19)，P < 0.000 1]，见图4E。 2.4.6 经皮氧分压共有3项研究比较经皮氧分压[10，12，16]，经过异质性检验提示各项研究间存在异质性(I2=63%，P=0.07)，分析原因可能是源于纳入研究中患者特征的差异有关，如年龄、病史、病变程度等。此外可能与不同研究中使用的间充质干细胞类型、治疗剂量及患者人群的差异有关，故采用随机效应模式分析。Meta结果显示，间充质干细胞组与对照组经皮氧分压比较存在统计学差异[SMD=1.62，95%CI(0.87，2.37)，P < 0.001]，见图4F。 2.4.7 无痛步行距离共有3项研究比较无痛步行距离[10，12，17]，经过异质性检验提示各项研究间存在异质性(I2=89%，P < 0.000 1)，故采用随机效应模式分析。Meta结果显示，间充质干细胞组与对照组无痛步行距离比较存在统计学差异[MD=131.81，95%CI(3.56，260.06)，P=0.04]，见图4G。"

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