Feasibility of stem cell therapy for renal ischemia/reperfusion injury: a systematic review based on animal experiments

doi:10.3969/j.issn.2095-4344.2078

Abstract

Abstract:

BACKGROUND: With the in-depth investigation of stem cells and better understanding of kidney ischemia/reperfusion injury, stem cell therapy for renal ischemia/reperfusion injury in animal experiments have been developed extensively, and have achieved certain advance. Therefore, it is necessary to conduct a systematic evaluation to explore the specific efficacy of stem cell therapy for renal ischemia/reperfusion injury.

OBJECTIVE: To systematically evaluate the effects of stem cells on the function and structure of the kidney and the immune function of the body and the feasibility of transformation into clinical practice based on the animal experiments.

METHODS: Databases of PubMed, Web of Science, Embase, CNKI, VIP and WanFang were searched by computer, and the search time was limited before May 2019. The literature was screened independently by two researchers, and the data were extracted. SYRCLE animal experiment bias risk assessment tool was used to evaluate the methodological quality of the study, and the evidence quality was evaluated using CERQual tool.

RESULTS AND CONCLUSION: Finally, 17 animal experiments were included, but there was great clinical heterogeneity among the studies. Therefore, we performed a qualitative description. Compared with the placebo group, the renal function (serum creatinine and blood urea nitrogen level), immune status and renal tissue injury in the stem cell therapy group were improved. But the evidence quality of the six outcome indexes was “low”, and there was a certain risk of bias in the study. The exact efficacy of stem cells and the need for further clinical research cannot be determined due to the problems in experimental design and quality of evidence. Therefore, prior to the inception of clinical trial, high-quality pre-clinical study is necessary to further evaluate the effect of stem cells on renal ischemia/reperfusion injury and the feasibility of clinical transformation to reduce the risk of clinical transformation.

Key words:

stem cells, universal cells, kidney, ischemia/reperfusion injury, animal experiment, systematic review, efficacy, clinical transformation

CLC Number:

Shang Zhizhong, Jiang Yanbiao, Yao Lan, Wang Anan, Wang Hongxia, Tian Yuanxin, Liu Dengrui, Ma Bin .

Feasibility of stem cell therapy for renal ischemia/reperfusion injury: a systematic review based on animal experiments [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(25): 4094-4100.

Figures/Tables 4

2.3 偏倚风险评估结果纳入研究的偏倚风险评估结果见图3。在纳入的17个随机对照实验中，仅1个研究报告了具体随机分组方法[30]，11个研究的基线特征均衡[14-16，18-23，25-26]，17个研究均未报告是否实施隐蔽分组。此外，所有研究均未报告结果评价过程中选择动物的方法；8个研究对实验动物进行随机化安置[15-16，18，21-23，25-26]；仅1个研究对动物饲养者和研究者施盲[18]。此外，4个研究存在与实验设计相关的偏倚风险[14，24-25，28]。 2.4 统计结果 2.4.1 结果概述纳入的17个研究中，均报告了血清肌酐水平和肾组织病理学改变；13个研究报告了血尿素氮水平[14，17，19-23，25-30]；6个研究报告了白细胞介素的表达水平[14，18-20，26，28]，5个研究报告了免疫细胞的浸润情况[15，18，20，28-29]；2个研究报告了白细胞分化抗原的表达水平[15，25]。此外，虽然绝大部分研究报告了血清肌酐和血尿素氮的水平，但其测定时点均存在差异，包括建模后 3 d[18-19，21-22，25，28-29]，14 d[14，24]，28 d等[30]；且各组干细胞种类、来源、治疗剂量和治疗持续时间亦存在较大差异。因此，导致无法对不同研究间的数据进行Meta分析。 2.4.2 血清肌酐水平、血尿素氮水平和肾组织病理学改变 17个研究报告了血清肌酐水平[14-30]，结果显示：相比于安慰剂组，干细胞治疗组的血清肌酐水平均有不同程度地降低(P < 0.05[15，17，19-20，22-28，30]， P < 0.01[16，29]， P < 0.001[14，18，21])；13个研究报告了血尿素氮水平[14，17，19-23，25-30]，结果显示：相比于安慰剂组，干细胞治疗组的血尿素氮水平均有不同程度地降低(P < 0.05[17，19-20，22-23，25-28，30]，P < 0.01[29]，P < 0.001[14，21])；17个研究报告了肾组织病理学改变[14-30]，结果显示：相比于安慰剂组，干细胞治疗组的肾组织病理学改变包括肾小管坏死和扩张、肾小管上皮细胞脱落或变性、管型形成、刷状缘丢失等均有减轻(组织病理学评分： P < 0.05[14-15，20，24-25，27，29-30]，P < 0.001[18，21，28]，还有定性报告结果[16-17，19，22-23，26])。 2.4.3 白细胞介素、白细胞分化抗原表达和免疫细胞的表达与浸润 6个研究报告了白细胞介素表达情况[14，18-20，26，28]，其中2个研究的结果均显示干细胞治疗组中抗炎因子白细胞介素10的表达水平高于安慰剂组[14，26]，差异有显著性意义(P < 0.05)；4个研究报告了促炎因子的表达水平[18-20，28]，结果显示干细胞治疗组白细胞介素6和白细胞介素1β的表达水平均低于安慰剂组[18-20，28]，差异有显著性意义(P < 0.05)。 2个研究报告了白细胞分化抗原表达情况[15，25]，结果显示干细胞组CD31和CD34的表达水平高于安慰剂组[25]，差异有显著性意义(P < 0.05)；干细胞组和安慰剂组CD204和CD206的表达水平差异无显著性意义(P > 0.1) [15]。 5个研究报告了免疫细胞的表达与浸润情况[15，18，20，28-29]，结果显示，安慰剂组巨噬细胞的浸润高于干细胞治疗组(P < 0.001[15，18，28]，还有研究为定性报告结果[29])；安慰剂组在淋巴细胞、中性粒细胞和T淋巴细胞浸润方面亦高于干细胞治疗组(P < 0.01[18]，P < 0.001[28]，还有研究为定性报告结果[29])。 "

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