Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury
Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury
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DOI：
10.1093/ndt/gfr015
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发表时间：
2011-05-01
影响因子：
6.1
通讯作者：
Camussi, Giovanni
中科院分区：
文献类型：
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作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
背景一些研究表明，间充质干细胞（MSC）逆转急性肾损伤（阿基）的旁分泌机制，而不是MSC转分化。我们最近证明，从MSC释放的微泡（MV）可以通过信使RNA和microRNA. Methods的水平转移解释这种旁分泌机制。将从骨髓间充质干细胞中分离的微血管静脉注射到大鼠体内（30 μ g/大鼠）。为了评价MV对缺血再灌注损伤（IRI）诱导的阿基的影响，将动物分为不同的组：正常大鼠（n = 4）、假手术大鼠（n = 6）、IRI大鼠（n = 6）、IRI + MV大鼠（n = 6）和IRI + RNase-MV大鼠（n = 6），并且在手术后第2天处死所有动物。将大鼠分为假手术组（n = 6）、IRI组（n = 6）、IRI + MV组（n = 6），术后6个月处死。我们发现，IRI后立即单次给予MV，通过抑制细胞凋亡和刺激肾小管上皮细胞增殖保护大鼠免受阿基。MV还显着减轻了肾功能损害。用RNA酶预处理MV以抑制其RNA货物消除了这些保护作用。此外，MVs通过减轻急性损伤也保护了以后的慢性肾脏疾病。从MSC释放的MV保护免于由缺血再灌注损伤诱导的阿基和随后的慢性肾损伤。这表明MV可以被开发为一种潜在的新的治疗方法。
Background. Several studies demonstrated that mesenchymal stem cells (MSCs) reverse acute kidney injury (AKI) by a paracrine mechanism rather than by MSC transdifferentiation. We recently demonstrated that microvesicles (MVs) released from MSCs may account for this paracrine mechanism by a horizontal transfer of messenger RNA and microRNA.Methods. MVs isolated from MSCs were injected intravenously in rats (30 mu g/rat) immediately after monolateral nephrectomy and renal artery and vein occlusion for 45 min. To evaluate the MV effects on AKI induced by ischaemia-reperfusion injury (IRI), the animals were divided into different groups: normal rats (n = 4), sham-operated rats (n = 6), IRI rats (n = 6), IRI + MV rats (n = 6), and IRI + RNase-MV rats (n = 6), and all animals were sacrificed at Day 2 after the operation. To evaluate the chronic kidney damage consequent to IRI, the rats were divided into different groups: sham-operated rats (n = 6) and IRI rats (n = 6), IRI + MV rats (n = 6), and all animal were sacrificed 6 months after the operation.Results. We found that a single administration of MVs, immediately after IRI, protects rats from AKI by inhibiting apoptosis and stimulating tubular epithelial cell proliferation. The MVs also significantly reduced the impairment of renal function. Pretreatment of MVs with RNase to inactivate their RNA cargo abrogated these protective effects. Moreover, MVs by reducing the acute injury also protected from later chronic kidney disease.Conclusion. MVs released from MSCs protect from AKI induced by ischaemia reperfusion injury and from subsequent chronic renal damage. This suggest that MVs could be exploited as a potential new therapeutic approach.