Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury.

Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury.
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DOI:
10.1093/ndt/gfq603
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发表时间:
2010-12
期刊:
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
影响因子:
--
通讯作者:
Pinkernell K
Pinkernell K
中科院分区:
其他
文献类型:
--
作者:
Feng Z;Ting J;Alfonso Z;Strem BM;Fraser JK;Rutenberg J;Kuo HC;Pinkernell K

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背景资料。急性肾损伤(AKI)是一个高死亡率和有限的因果治疗的主要临床问题。细胞疗法的使用已被认为是改善AKI病程和结局的一种潜在方式。方法:研究方法。我们研究了新鲜分离的、未培养的脂肪组织来源的干细胞和再生细胞(ADRC)在AKI大鼠缺血再灌注(I-R)模型中冷冻保存前后可能的肾脏保护作用。结果。我们发现ADRC治疗显著降低了死亡率(存活率分别为100%和57%,ADRC与对照组相比分别为57%),并显著降低了血肌酐(第3天的Scr分别为3.03±1.58和7.37±2.32 mg/dL,ADRC与对照组相比)。组织学分析进一步证实,肾小管内管型形成显著减少,急性肾小管上皮细胞坏死减轻,巨噬细胞浸润减轻。此外,ADRC组CXCL2和IL-6的RNA表达减少,这可能是巨噬细胞募集减少的原因。使用冷冻保存的ADRC可导致同样高的存活率(90%比对照组的33%)和相似的改善肾功能(第3天的Scr:对照组:4.64±2.43比7.24±1.40 mg/dL)。结论。总而言之,这些结果提示ADRC疗法在AKI患者中具有潜在的临床作用。重要的是,ADRC的冷冻保存可以为在有计划的干预期间AKI高危患者提供一种自体治疗策略。
Background. Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited causal treatments. The use of cell therapy has been suggested as a potential modality to improve the course and outcome of AKI. Methods. We investigated the possible renoprotection of freshly isolated, uncultured adipose tissue-derived stem and regenerative cells (ADRCs) before and after cryopreservation in a rat ischemia–reperfusion (I–R) model of AKI. Results. We demonstrated that ADRC therapy drastically reduced mortality (survival 100% vs. 57%, ADRC vs. controls, respectively) and significantly reduced serum creatinine (sCr on Day 3: 3.03 ± 1.58 vs. 7.37 ± 2.32 mg/dL, ADRC vs. controls, respectively). Histological analysis further validated a significantly reduced intratubular cast formation, ameliorated acute tubular epithelial cell necrosis and mitigated macrophage infiltration. Furthermore, a reduced RNA expression of CXCL2 and IL-6 was found in the ADRC group which could explain the reduced macrophage recruitment. Use of cryopreserved ADRCs resulted in an equally high survival (90% vs. 33% in the control group) and similarly improved renal function (sCr on Day 3: 4.64 ± 2.43 vs. 7.24 ± 1.40 mg/dL in controls). Conclusions. Collectively, these results suggest a potential clinical role for ADRC therapy in patients with AKI. Importantly, cryopreservation of ADRCs could offer an autologous treatment strategy for patients who are at high risk for AKI during planned interventions.
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