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

急性肾损伤(AKI)严重影响住院患者的预后。在过去的20年里，与AKI相关的死亡率并没有大幅下降。因此，迫切需要新的治疗策略来改善AKI的预后。近年来开展的OWN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，人类AKI的EEOC治疗可能与几个问题有关。(I)第一个问题与给药的确切时间点有关。细胞应该在肾脏再灌流时注射，但几乎不可能准确预测肾脏缺血。(2)用于肾脏修复的细胞应大量供应。然而，EEOC浓缩通常需要5-7天。(Iii)第三个问题与免疫兼容性有关。在最佳情况下，EEOCs应与寄主有机体分离。在大多数情况下，AKI在合并多种疾病的患者中发生。已有文献证明，动脉粥样硬化、脓毒症和几种自身免疫介导的疾病显著损害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，EEOCs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移植到临床AKI的治疗中。

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.