Early Endothelial Outgrowth Cell-mediated mechanisms of postischemic renoprotection as new therapeutic approach to treat AKI

早期内皮生长细胞介导的缺血后肾脏保护机制作为治疗 AKI 的新方法

• 批准号: 284183331
• 负责人: Professor Dr. Daniel Patschan
• 金额: --
• 依托单位: Center for Biostructural Imaging of Neurodegeneration (BIN)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/284183331?language=en
• 关键词: Early; Endothelial; Outgrowth; Cell; mediated

Acute kidney injury (AKI) significantly worsens prognosis of hospitalized patients. AKI-associated mortality has not substantially been decreased over the last 20 years. Thus, new therapeutic strategies to improve AKI outcomes are urgently needed. Own investigations performed in recent years showed systemic early Endothelial Outgrowth Cell (eEOC) administration as effective option in murine AKI. Nevertheless, eEOC therapy of human AKI may be associated with several problems. (I) The first problem is related to the exact time point of cell administration. Cells should be injected at the time of kidney reperfusion but it is nearly impossible to exactly predict renal ischemia. (II) The cells being administered for kidney repair should be available in large numbers. However, eEOC enrichment usually requires 5-7 days. (III) The third problem is related to immunological compatibility. In an optimal situation, eEOCs should be isolated from the host organism. In most cases AKI evolves in patients with numerous comorbidities. It has been documented that atherosclerosis, sepsis, and several autoimmune-mediated disorders significantly impair eEOC competence. Thus, it can not be assumed that eEOC treatment is equally effective in different individuals suffering from certain inflammatory and non-inflammatory diseases. Therefore, eEOCs will most likely not serve as therapeutic tool in human AKI per se. However, the mechanisms by which the cells act within the perivascular microenvironment should be transferable into the management of clinical AKI.

急性肾损伤（AKI）显着恶化住院患者的预后。过去 20 年来，AKI 相关死亡率并未大幅下降。因此，迫切需要新的治疗策略来改善 AKI 结局。近年来进行的研究表明，全身性早期内皮生长细胞 (eEOC) 给药是治疗小鼠 AKI 的有效选择。然而，eEOC 治疗人类 AKI 可能会带来几个问题。 （一）第一个问题与细胞给药的具体时间点有关。细胞应在肾脏再灌注时注射，但几乎不可能准确预测肾缺血。 (II) 用于肾脏修复的细胞应该是大量可用的。然而，eEOC 富集通常需要 5-7 天。 （三）第三个问题与免疫相容性有关。在最佳情况下，eEOC 应与宿主生物体分离。在大多数情况下，AKI 是在患有多种合并症的患者中发生的。据记载，动脉粥样硬化、脓毒症和几种自身免疫介导的疾病会显着损害 eEOC 能力。因此，不能认为 eEOC 治疗对于患有某些炎症和非炎症性疾病的不同个体同样有效。因此，eEOC 本身很可能不会作为人类 AKI 的治疗工具。然而，细胞在血管周围微环境中的作用机制应该可以转移到临床 AKI 的治疗中。