Abstract 16501: Intravenous Administration of Neonatal Mesenchymal Stem Cells Mediates Functional Recovery in a Renal Ischemia-reperfusion Injury Rodent Model

Abstract

Introduction: The prevalence of acute kidney injury in cardiac surgery patients is up to 30%. However, treatments to facilitate kidney recovery are mainly limited to supportive care. In preclinical studies, stem cell therapy using adult Mesenchymal Stem Cells (aMSCs) has reduced kidney damage through the secretion of paracrine factors. Previously, we have established that our neonatal Mesenchymal Stem Cells (nMSCs) have a more potent anti-inflammatory and pro-angiogenic secretome profile than aMSCs. Hypothesis: Intravenous administration of nMSCs and their secretome (total conditioning media) will diminish kidney injury in a renal ischemia-reperfusion injury rodent model. Methods: Six to seven-week-old Brown-Norway rodents underwent bilateral renal clamping to induce 90-minute ischemia. After removal of the clamps and renal reperfusion, the rodents were injected with 100 uL of PlasmaLyte A (control; n=7), an nMSC suspension (10 million cells/kg; n=6), or a total conditioning media (TCM) suspension (10 mg/kg; n=6) via their lateral tail vein. Results: One day after nMSC and TCM treatment, both blood urea nitrogen (116.08 ± 12.02 vs 149.41 ± 9.26 mg/dL; *p=0.0434 and 111.34 ± 9.54 vs 149.41 ± 9.26 mg/dL; *p=0.0174, respectively) and blood creatinine (0.75 ± 0.074 vs 1.25 ± 0.18 mg/dL; **p=0.0028 and 0.76 ± 0.06 vs 1.25 ± 0.18 mg/dL; **p=0.0030, respectively) levels were significantly reduced compared to after PlasmaLyte A injection. Associated decreases in pro-apoptotic signaling molecules (CASP8, BAK, and BAD) and increases in anti-apoptotic signaling molecules (pAKT, SOD2, and BCL2) are being investigated. Conclusions: nMSC and TCM treatment via intravenous injection showed indications of a reduction in kidney injury. This therapy should be further investigated for use in select cardiac surgery patients.