ABSTRACT
Background/Aims@#Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. @*Methods@#Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. @*Results@#Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. @*Conclusions@#The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.
ABSTRACT
PURPOSE: This report introduces a new method for tensioning the remnant PCL with a reconstruction of the anterolateral (AL) bundle of the PCL using a modified tibial inlay technique with an assessment of the outcome of this method in chronic PCL injury. MATERIALS AND METHODS: From January 1998 to August 2003, eighty six patients was underwent tensioning of a laxed remnant PCL with a reconstruction of the anterolateral bundle of the PCL. Of these, fifty two patients who were followed up for more than 2 years were evaluated. Tensioning was performed using a distal transfer of the tibial attachment with the posteromedial approach in the supine position. The AL bundle of the PCL was reconstructed with 4 bundles of a hamstring autograft or tibialis anterior tendon allograft. The stability was assessed objectively using stress radiographs with the Telos(R) device and the maximal manual test with the KT-1000 arthrometer. The clinical results were assessed by the IKDC (International Knee Documentation Committee) and OAK (Orthopadische Arbeitsgruppe Knie) scores. The posterior drawer test, varus stress test, posterolateral drawer test and dial test in 30 degrees and 90 degrees flexion were performed for a physical examination. RESULTS: The average side to side difference of the posterior tibial translation in stress radiographs with the Telos(R) device decreased from 10.4+/-2.0 mm to 2.2+/-1.0 mm. The average side to side difference in the maximal manual test with the KT-1000 arthrometer also decreased from 8.2+/-1.5 mm to 1.9+/-1.0 mm. The final IKDC score was A in eleven (21.2%), B in thirty-five (67.3%) and C in six (11.5%) patients. The average OAK score improved from 64.3+/-8.9 to 90.8+/-7.2. CONCLUSION: Tensioning of the laxed remnant PCL with a reconstruction of the AL bundle in chronic PCL injuries showed good clinical results and excellent posterior stability.