Short-term preconditioning enhances the therapeutic potential of adipose-derived stromal/stem cell-conditioned medium in cisplatin-induced acute kidney injury

• Published in: Experimental cell research 2016-03, Vol.342 (2), p.175-183
• Main Authors: Overath, Jürgen M., Gauer, Stefan, Obermüller, Nicholas, Schubert, Ralf, Schäfer, Richard, Geiger, Helmut, Baer, Patrick C.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - prevention & control; Adipose Tissue, White - pathology; Adult Stem Cells - physiology; Adult Stem Cells - transplantation; Animals; Antineoplastic Agents - toxicity; Cell Culture Techniques; Cells, Cultured; Cellular biology; Cisplatin - toxicity; Conditioned medium; Culture Media, Conditioned; Hypoxia; Interleukins - metabolism; Interleukins - secretion; Kidney diseases; Kidney regeneration; Mesenchymal Stromal/stem cells; Mice, Inbred C57BL; Preconditioning; Renal failure; Stem cells
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2016.03.002

The development of new strategies to preserve renal function after acute kidney injury (AKI) is necessary due to limited clinical intervention options. The organ-protective effects of mesenchymal stromal/stem cells (MSCs) and their conditioned medium (CM) have been investigated demonstrating that both separately promoted tubular recovery and ameliorated the outcome of AKI. Nevertheless, strategies to optimise the regenerative potential of both are highly needed. Here we investigated the effects of CM from adipose-derived MSCs (ASCs) preincubated in a hypoxic environment (Hyp). Protective factors were investigated by PCR analysis and a protein array in vitro. The expression of 64 of the 308 proteins assayed was found to be more than two-fold increased after Hyp. CM of Hyp-pretreated ASCs (pCM) was used to enhance regeneration in a mouse model of cisplatin-induced AKI (cisAKI). Renal function was assessed by measurements of markers for AKI and serum cytokine levels. The pCM significantly ameliorated serum creatinine and neutrophil gelatinase-associated lipocalin values, and also the levels of inflammatory cytokines IL-1β and IL-6 in the serum of mice with AKI. Our work clearly showed that a Hyp preconditioning significantly increases the release of protective factors in ASCs and enhances the therapeutic effects of CM in cisAKI in mice. •Upregulation of regenerative factors was gained after hypoxic preconditioning in vitro.•pCM significantly improves the levels of IL-1ß and IL-6 in the serum after AKI in vivo.•pCM significantly lowers the increase of serum Creatinine and N-Gal after AKI in vivo.•In summary pCM shows significant more improvement after AKI compared to CM or control.