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

• Applicant: Professor Dr. Daniel Patschan
• Subject Area: Nephrology
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 284183331

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.

• DFG Programme: Research Grants
• Cooperation Partner: Professor Dr. Hassan Dihazi