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

急性肾损伤（AKI）显著恶化住院患者的预后。在过去的20年里，aki相关的死亡率并没有显著下降。因此，迫切需要新的治疗策略来改善AKI的预后。近年来进行的自己的研究表明，系统性早期内皮生长细胞（eEOC）给药是小鼠AKI的有效选择。然而，eEOC治疗人类AKI可能与几个问题有关。（一）第一个问题与细胞给药的确切时间点有关。细胞应在肾再灌注时注射，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有大量可用。然而，eEOC的富集通常需要5-7天。（三）第三个问题与免疫相容性有关。在最佳情况下，eeoc应从宿主生物中分离出来。在大多数情况下，AKI在有许多合并症的患者中发展。有文献表明，动脉粥样硬化、败血症和一些自身免疫介导的疾病会显著损害eEOC的能力。因此，不能假设eEOC治疗对患有某些炎症性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的管理中。

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.