title: Short-term preconditioning enhances the therapeutic potential of adipose-derived stromal/stem cell-conditioned medium in cisplatin-induced acute kidney injury.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: juergen.overath@kgu.de.
authors.forename: Jürgen M
authors.initials: JM
authors.lastname: Overath
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: gauer@em.uni-frankfurt.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gauer
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: obermueller@em.uni-frankfurt.de.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Obermüller
authors.affiliation: Department of Paediatrics, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: ralf.schubert@kgu.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, Cell Therapeutics & Cell Processing, Goethe University, 60528 Frankfurt/M., Germany. Electronic address: r.schaefer@blutspende.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Schäfer
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: h.geiger@em.uni-frankfurt.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Geiger
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Goethe-University, 60590 Frankfurt/M., Germany. Electronic address: patrick.baer@kgu.de.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Baer
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D052436:Adipose Tissue, White / Q000473:pathology; D053687:Adult Stem Cells / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D017077:Culture Media, Conditioned; D007378:Interleukins / Q000378:metabolism; D008810:Mice, Inbred C57BL
chemical_list: D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D007378:Interleukins; D002945:Cisplatin
keywords: Conditioned medium; Hypoxia; Kidney regeneration; Mesenchymal Stromal/stem cells; Preconditioning; Renal failure