Ullah, Md MahbubCollett, Jason A.Monroe, Jacob C.Traktuev, DmitryColeman, MichaelMarch, Keith L.Basile, David P.2024-07-082024-07-082024-04-24Ullah MM, Collett JA, Monroe JC, et al. Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury. Stem Cell Res Ther. 2024;15(1):119. Published 2024 Apr 24. doi:10.1186/s13287-024-03736-xhttps://hdl.handle.net/1805/42058Background: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. Methods: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. Results: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. Conclusions: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.en-USAttribution 4.0 InternationalAKICKDTh17 cellsMacrophagesKidney repairArticle