Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury

Stem Cell Res Ther. 2024 Apr 24;15(1):119. doi: 10.1186/s13287-024-03736-x.


Background: 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.

Keywords: AKI; CKD; Kidney repair; Macrophages; Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Acute Kidney Injury* / therapy
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Animals
  • Humans
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Injections, Subcutaneous
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / therapy
  • Secretome / metabolism
  • Stromal Cells / metabolism