Blondeel Joris, Gilbo Nicholas, De Bondt Stijn, Monbaliu Diethard
Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.
Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.
Stem Cell Rev Rep. 2023 Oct;19(7):2225-2250. doi: 10.1007/s12015-023-10573-7. Epub 2023 Aug 7.
The possible beneficial effects of stem cell-derived EV on ischemia-reperfusion injury (IRI) in organ transplantation have been frequently investigated; however, the source of EV, as well as the methods of isolation and administration vary widely. We conducted a systematic review to summarize current pre-clinical evidence on stem cell-derived EV therapy for IRI of transplantable organs.
PubMed, Embase and Web of Science were searched from inception until August 19th, 2022, for studies on stem cell-derived EV therapy for IRI after heart, kidney, liver, pancreas, lung and intestine transplantation. The Systematic Review Center for Laboratory animal Experiments (SYRCLE) guidelines were followed to assess potential risk of bias.
The search yielded 4153 unique articles, of which 96 were retained. We identified 32 studies on cardiac IRI, 38 studies on renal IRI, 21 studies on liver IRI, four studies on lung IRI and one study on intestinal IRI. Most studies used rodent models of transient ischemic injury followed by in situ reperfusion. In all studies, EV therapy was associated with improved outcome albeit to a variable degree. EV-therapy reduced organ injury and improved function while displaying anti-inflammatory-, immunomodulatory- and pro-regenerative properties.
A multitude of animal studies support the potential of stem cell-derived EV-therapy to alleviate IRI after solid organ transplantation but suffer from low reporting quality and wide methodological variability. Future studies should focus on determining optimal stem cell source, dosage, and timing of treatment, as well as long-term efficacy in transplant models.
干细胞衍生的细胞外囊泡（EV）对器官移植中缺血再灌注损伤（IRI）可能具有的有益作用已得到广泛研究；然而，EV的来源以及分离和给药方法差异很大。我们进行了一项系统综述，以总结目前关于干细胞衍生的EV治疗可移植器官IRI的临床前证据。
检索PubMed、Embase和Web of Science数据库，检索时间从建库至2022年8月19日，以查找关于干细胞衍生的EV治疗心脏、肾脏、肝脏、胰腺、肺和肠道移植后IRI的研究。遵循实验动物系统综述中心（SYRCLE）指南评估潜在的偏倚风险。
检索共获得4153篇独特文章，其中96篇被保留。我们确定了32项关于心脏IRI的研究、38项关于肾脏IRI的研究、21项关于肝脏IRI的研究、4项关于肺IRI的研究和1项关于肠道IRI的研究。大多数研究使用短暂性缺血损伤后原位再灌注的啮齿动物模型。在所有研究中，EV治疗均与不同程度的预后改善相关。EV治疗减少了器官损伤，改善了功能，同时表现出抗炎、免疫调节和促再生特性。
大量动物研究支持干细胞衍生的EV治疗减轻实体器官移植后IRI的潜力，但报告质量较低，方法学差异较大。未来的研究应侧重于确定最佳的干细胞来源、剂量和治疗时机，以及在移植模型中的长期疗效。
