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肾移植中间质基质细胞的诱导治疗:荟萃分析。

Induction therapy with mesenchymal stromal cells in kidney transplantation: a meta-analysis.

机构信息

Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Institute of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

出版信息

Stem Cell Res Ther. 2021 Mar 1;12(1):158. doi: 10.1186/s13287-021-02219-7.

Abstract

OBJECTIVE

The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications.

METHODS

PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT.

RESULTS

Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46-0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41-1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95-1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21-1.38, P = 0.2) and renal graft function at 1 month (MD = -1.56, 95% CI: - 14.2-11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: - 5.63-5.93, p = 0.96), 6 months (MD = - 1.95, 95% CI: - 9.87-5.97, p = 0.63), and 12 months (MD = - 1.13, 95% CI: - 7.16-4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable.

CONCLUSION

Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.

摘要

目的

本荟萃分析旨在评估间充质干细胞(MSCs)与肾移植(KT)诱导治疗中传统方案相比的治疗效果,特别是 MSC 输注的安全性、MSCs 作为诱导治疗药物的实用性以及移植后的并发症。

方法

检索 PubMed、Embase、EBSCO、Ovid 和 Cochrane 图书馆,纳入比较 MSCs 与 KT 诱导治疗中传统方案的前瞻性临床试验。

结果

共纳入 4 项试验,总计 197 例患者。汇总结果显示,MSC 治疗组 1 年感染率低于传统治疗组(RR=0.65,95%CI:0.46-0.9,P=0.01)。两组 1 年急性排斥反应(AR)率(RR=0.77,95%CI:0.41-1.45,P=0.42)、1 年移植物存活率(RR=0.99,95%CI:0.95-1.03,P=0.74)、延迟移植物功能(DGF)率(RR=0.54,95%CI:0.21-1.38,P=0.2)和术后 1 个月(MD=-1.56,95%CI:-14.2-11.08,p=0.81)、3 个月(MD=0.15,95%CI:-5.63-5.93,p=0.96)、6 个月(MD=-1.95,95%CI:-9.87-5.97,p=0.63)和 12 个月(MD=-1.13,95%CI:-7.16-4.89,p=0.71)的肾功能无显著差异。亚组分析显示,低剂量钙调磷酸酶抑制剂(CNI)组和标准剂量 CNI 组间 1 年 AR 率、1 年移植物存活率、DGF 率和术后 12 个月的移植物肾功能无显著差异,提示 CNI 成功节约与 MSC 治疗相结合具有潜在益处。此外,当 MSCs 作为替代治疗而非附加治疗,或使用同种异体 MSCs 而非自体 MSCs 时,上述所有结果均相似。

结论

在 KT 受者中,MSC 诱导治疗在短期内是安全的,并且具有与传统方案相似的免疫反应调节作用。然而,就长期效果而言,正如 1 年感染率和 CNI 节约潜力所表明的那样,MSC 治疗具有显著优势。然而,这些优势应该在更多设计良好、多中心、大样本量和长随访期的随机对照试验(RCT)中进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b16/7923637/680ad27243f2/13287_2021_2219_Fig1_HTML.jpg

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