A Systematic Review of Preclinical Studies on the Therapeutic Potential of Mesenchymal Stromal Cell-Derived Microvesicles
A Systematic Review of Preclinical Studies on the Therapeutic Potential of Mesenchymal Stromal Cell-Derived Microvesicles
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DOI：
10.1007/s12015-014-9545-9
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发表时间：
2015-02-01
影响因子：
4.8
通讯作者：
Allan, David S.
中科院分区：
文献类型：
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作者：
Akyurekli, Celine;Le, Yevgeniya;Allan, David S.
间充质基质细胞（MSCs）的治疗潜力可能主要由细胞内小体释放的微泡（MV）中含有的旁分泌因子介导。一项系统的对照干预性动物研究进行了回顾，以确定器官损伤模型，其中msc来源的微泡治疗的临床翻译最有希望作为再生治疗。系统检索电子数据库（MEDLINE、EMBASE、PUBMED），共检索到190篇已发表文章。在筛选合格性后，共有17项对照研究对mscs衍生的mv作为疾病动物模型的治疗干预进行了全面审查、质量评估和数据提取。13项研究探讨了器官损伤后的再生潜力。急性肾损伤研究6项，心肌梗死及再灌注损伤研究4项，后肢缺血研究1项，肝损伤研究1项，肺缺氧损伤研究1项。四项研究探讨了骨髓间质干细胞衍生的mv在抑制肿瘤生长方面的免疫学作用。12项研究（71%）提供了关于分配到实验组或对照组的动物数量的明确信息。5项研究（29%）将动物随机分配到治疗组或对照组，只有1项研究（6%）报告了盲法。在8项研究中，治疗干预涉及分离外泌体（40-100 nm），而9项研究测试未分离的微囊泡（< 1,000 nm）。在组织再生的研究中，所有13项研究都报告了用msc来源的mv治疗至少改善了一个与器官功能障碍相关的主要/临床参数。评估肿瘤生长抑制的4项研究中有3项报告了益处。在临床前研究中，使用间质干细胞衍生的mv与损伤后器官功能的改善密切相关，可能有助于抑制肿瘤生长。在治疗分配报告、随机化和盲法方面，临床前研究质量的提高将加速临床试验的进展，这些临床试验应评估这种治疗方法在人体中的可行性和安全性。
The therapeutic potential of mesenchymal stromal cells (MSCs) may be largely mediated by paracrine factors contained in microvesicles (MV) released from intracellular endosomes. A systematic review of controlled interventional animal studies was performed to identify models of organ injury where clinical translation of MSC-derived microvesicle therapy appears most promising as regenerative therapy.A total of 190 published articles were identified in our systematic search of electronic databases (MEDLINE, EMBASE, PUBMED). After screening for eligibility, a total of 17 controlled studies testing MSC-derived MVs as therapeutic interventions in animal models of disease underwent comprehensive review, quality assessment, and data extraction.Thirteen studies addressed the regenerative potential following organ injury. Six studies were included on acute kidney injury, 4 on myocardial infarction and reperfusion injury, 1 on hind limb ischemia, 1 on liver injury, and 1 on hypoxic lung injury. Four studies addressed immunological effects of MSC-derived MVs on inhibiting tumor growth. Twelve studies (71 %) provided explicit information regarding the number of animals allocated to treatment or control groups. Five studies (29 %) randomly assigned animals to treatment or control groups and only 1 study (6 %) reported on blinding. Therapeutic intervention involved isolation of exosomes (40-100 nm) in eight studies, while nine studies tested unfractionated microvesicles (< 1,000 nm). In studies of tissue regeneration, all 13 reported that treatment with MSC-derived MVs improved at least one major/clinical parameter associated with organ dysfunction. Three of 4 studies evaluating the inhibition of tumor growth reported benefit.In preclinical studies, the use of MSC-derived MVs is strongly associated with improved organ function following injury and may be useful for inhibiting tumor growth. Improved preclinical study quality in terms of treatment allocation reporting, randomization and blinding will accelerate needed progress towards clinical trials that should assess feasibility and safety of this therapeutic approach in humans.