Comparison of muscle-derived stem

Abstract

Introduction: The skeletal muscle-derived stem/progenitor cells (MDSPCs) have been thoroughly investigated in preclinical studies. However, the therapeutic potential of MDSPCs for acute kidney injury (AKI) has only been evaluated by our research group. We aimed to compare MDSPCs with bone marrow mesenchymal stem cells (BM-MSCs) and to evaluate their feasibility for the treatment of AKI. Material and methods: Rats were randomly assigned to one of four groups: healthy controls, AKI group, AKI treated with MDSPCs, AKI treated with BMMSCs. AKI was induced by gentamicin (80 mg/kg/ day; i.p.) for 7 consecutive days. PKH-26-labeled MDSPCs and BM-MSCs (1 9 106 cells/animal) were injected intravenously 24 h after the last gentamicin injection. Physiological and histological kidney parameters were determined on day 0, 8, 14, 21, 28, 35 (6 animals per time point). Results: Both, MDSPCs and BM-MSCs accelerated functional kidney recovery and regeneration, as PARP are downstream intracellular effectors of rt-PA. Rt-PA also altered the morphology of bEnd.3 cells that were furthermore no longer confluent. Plasmin was implicated in these changes, unlike p38-MAPK and PARP. This study demonstrates that rt-PA induces the production of microparticles by cerebral endothelial cells, through plasmin, p38-MAPK and PARP pathways. Determining the phenotype of these EMPs could be of particular interest to clarify their role on the endothelium in ischemic conditions.