Limited Immune-Modulating Activity of Porcine Mesenchymal Stromal Cells Abolishes Their Protective Efficacy in Acute Kidney Injury
Limited Immune-Modulating Activity of Porcine Mesenchymal Stromal Cells Abolishes Their Protective Efficacy in Acute Kidney Injury
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DOI：
10.1089/scd.2009.0494
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发表时间：
2010-05-01
影响因子：
4
通讯作者：
Lange, Claudia
中科院分区：
文献类型：
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作者：
Brunswig-Spickenheier, Baerbel;Boche, Janna;Lange, Claudia
我们之前证明，在大鼠肾缺血/再灌注损伤（IRI）后给予间充质基质细胞（MSC）可以保护肾功能并通过复杂的旁分泌机制加速修复。在这里，我们研究了猪 IRI 模型中 MSC 的肾脏保护作用，这可能与人类急性肾损伤 (AKI) 相关。患有双侧 IRI 的雌性猪组被注入自体或雄性同种异体 MSC。没有观察到急性或晚期并发症，但出乎意料的是，间充质干细胞治疗对肾功能和组织学也没有有益影响。在体外，我们证明了啮齿动物、人类和猪 MSC 之间存在大量功能和表型重叠，所有这些 MSC 均表现出三系分化、特征性抗原谱以及肾脏保护性血管内皮生长因子 (VEGF)-A 和胰岛素样生长因子-1 (IGF-1) 的分泌。然而，与人类 MSC 形成鲜明对比的是，猪 MSC 未能抑制混合淋巴细胞反应 (MLR) 并诱导促炎性白细胞介素 6 (IL-6) 的大量产生。总之，与啮齿动物模型相比，用 MSC 治疗猪 IRI 并不能起到肾脏保护作用。我们得出结论，这是由于猪 MSC 发挥的免疫调节作用不足，进一步证明 MSC 成功治疗 IRI 关键取决于其抗炎作用。因此，用 MSC 治疗 AKI 对于研究这种大型动物模型的潜在机制并没有提供任何信息。然而，我们预计，用免疫调节间充质干细胞治疗人类肾脏 IRI 将与啮齿动物模型一样有效。
We demonstrated previously that administration of mesenchymal stromal cells (MSCs) after renal ischemia/reperfusion injury (IRI) in rats protected renal function and hastened repair through complex paracrine mechanisms. Here we investigated kidney-protective actions of MSCs in a porcine IRI model that may have relevance to human acute kidney injury (AKI). Groups of female pigs with bilateral IRI were infused with autologous or male allogeneic MSCs. No acute or late complications were observed, but unexpectedly, MSC therapy also had no beneficial effects on kidney function and histology. In vitro, we demonstrated substantial functional and phenotypic overlaps between rodent, human, and porcine MSCs, all of which exhibited trilineage differentiation, characteristic antigen profiles, and secretion of renoprotective vascular endothelial growth factor (VEGF)-A and insulin-like growth factor-1 (IGF-1). However, in striking contrast to human MSCs, porcine MSCs failed to inhibit the mixed lymphocyte reaction (MLR) and induced robust production of proinflammatory interleukin-6 (IL-6). In summary, in contrast to rodent models, treatment of porcine IRI with MSCs was not kidney-protective. This, we conclude, is due to the fact that porcine MSCs exert inadequate immune-modulating effects, further demonstrating that successful therapy of IRI with MSCs critically depends on their anti-inflammatory actions. As a consequence, treatment of AKI with MSCs is not informative regarding the investigation of the underlying mechanisms in this large animal model. We expect, however, that the treatment of human IRI of the kidney with immune-modulating MSCs will be as effective as in rodent models.