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

急性肾损伤（阿基）严重影响住院患者的预后。在过去20年中，AKI相关死亡率并未大幅下降。因此，迫切需要改善阿基结局的新治疗策略。近年来进行的研究表明，全身早期内皮生长细胞（eEOC）给药是鼠阿基的有效选择。然而，人阿基的eEOC疗法可能与几个问题相关。(I)第一个问题与细胞施用的确切时间点有关。细胞应该在肾再灌注时注射，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大量可用。然而，eEOC富集通常需要5-7天。(III)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。在大多数情况下阿基在患有多种合并症的患者中发展。已经证明动脉粥样硬化、脓毒症和几种自身免疫介导的疾病显著损害eEOC能力。因此，不能假设eEOC治疗在患有某些炎性和非炎性疾病的不同个体中同样有效。因此，eEOC本身很可能不作为人类阿基的治疗工具。然而，细胞在血管周围微环境中发挥作用的机制应该可以转移到临床阿基的管理中。

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.