The In Vivo Effects of Ischemic Renal Tissue Conditioned Medium Mesenchymal Stem Cell Therapy in Acute Ischemic KidneyInjury

Background and Aim: Renal diseases are a common condition in thegeneral population and resulted in significant morbidity and mortality.Acute kidney injury (AKI) occurred in 8-16% of hospital admissions. Theresults of recent studies showed mesenchymal stem cells (MSCs) canimprove renal ischemia-reperfusion injury (IRI), glycerol and cisplatinummodel of AKI, glomerulonephritis model, Alport’s syndrome, and diabeticnephropathy. The aim of this study was to test the therapeutic potentialeffects of administration of conditioned medium (CM) treated MSCs,immediately after reflow in a rat model of IRI/AKI.Methods: MSCs were generated from the femur and tibia of 6 weeksold male Wistar rats. MSCs morphology and phenotype were confirmedby differentiation and FACS analysis. Passage 3-4 was used in allexperiments. CM was prepared from the supernatant of rat kidney thatundergoes 40 minutes of ischemia. MSCs were treated by 50 μg/mL CMfor 24 hours. Adult male Wistar rats weighing 250–300 g were used.The rats were randomly assigned to the following groups: IRI, IRI withMSC treated, and IRI with CM-MSC treated. After laparotomy, renalpedicles were clamped for 40 minutes, and after reflow, ~2×106 MSCswere injected systemically via the supra-renal aorta. Blood samples werecollected at baseline and day 1 post-IRI.Results: MSCs were confirmed by morphology, differentiation and FACSanalysis. 40 min of clamping in animals led to severe renal insufficiency,as evidenced by a rise in serum Cr to 3.41±0.22 mg/dL and serum BUNto 86.8±6.65 mg/dL in IRI rats at 24 h post-ischemia. Animals infusedwith MSC and CM-MSCs, had significantly lower serum Cr, 1.04±0.08and 0.98±0.09 mg/dL and BUN levels, 58.9±3.96 and 55.2±6.65 mg/dLrespectively at 24 hours after cell injection compared with IRI animals.However, the serum Cr and BUN levels were slightly decreased in CMMSCstreated animals compared with MSC treated; the differences werenot significant.Conclusion: This work provides further evidence that MSCs might havesubstantial protective effects in IRI/AKI rat model. Accordingly, withour results, there might not be any transdifferentiation events of MSCswithin the first day and the protective effects occur via differentiationindependentmechanisms. The CM contains substances that affect themigration of MSCs toward the injured tissue. Take all, our findingsshowed the kidney-protective effect of MSCs in IRI/AKI experimentalmodel. We also witnessed the effects of ischemic renal tissue on in vitroMSCs properties. We believe more studies are required to clarify themechanism responsible for this recovery.

کلیدواژه ها:

Mesenchymal stem cell ، Acute kidney injury ، Conditionedmedium ، Cell therapy