Mechanisms of kidney repair by human mesenchymal stromal cells after ischemia: A comprehensive view using label‐free MS^E

Abstract

Acute kidney injury (AKI) is one of the more frequent and lethal pathological conditions seen in intensive care units. Currently available treatments are not totally effective but stem cell-based therapies are emerging as promising alternatives, especially the use of mesenchymal stromal cells (MSC), although the signaling pathways involved in their beneficial actions are not fully understood. The objective of this study was to identify signaling networks and key proteins involved in the repair of ischemia by MSC. Using an in vitro model of AKI to investigate paracrine interactions and label-free high definition 2D-NanoESI-MS(E) , differentially expressed proteins were identified in a human renal proximal tubule cell lineage (HK-2) exposed to human MSC (hMSC) after an ischemic insult. In silico analysis showed that hMSC stimulated antiapoptotic activity, normal ROS handling, energy production, cytoskeleton organization, protein synthesis, and cell proliferation. The proteomic data were validated by parallel experiments demonstrating reduced apoptosis in HK-2 cells and recovery of intracellular ATP levels. qRT-PCR for proteins implicated in the above processes revealed that hMSC exerted their effects by stimulating translation, not transcription. Western blotting of proteins associated with ROS and energy metabolism confirmed their higher abundance in HK-2 cells exposed to hMSC.

Adipose-Derived Mesenchymal Stromal Cells Under Hypoxia: Changes in Extracellular Vesicles Secretion and Improvement of Renal Recovery after Ischemic Injury

“…transcription and translation regulation, cytoskeleton reorganization and protein folding. Some of these processes were also modulated in renal cells by the paracrine actions of BM-MSCs [41], supporting the importance of EVs secretion in the interaction between MSCs and renal cells. Interestingly, EV CTR and EV HPX also have specific signatures by modulating exclusive groups of proteins.…”

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

“…These processes have been involved in the regulation of energy metabolism of damaged tubular epithelial cells by MSC treatment. 37 Moreover, AKI damage was associated with the upregulation of genes involved in inflammation, ECM-receptor interaction, The relative expression (RQ) of miRNAs in EV-Dsh was defined as FC evaluated as 2 2DDCt with respect to the reference sample (EV-CTRL) as described in Concise Methods (n=4 in each group; P,0.05).…”

Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics

“…The levels of mRNA after MTB infection did not correlate with the proteins level. A similar result demonstrated that when the most induced proteins in human mesenchymal stromal cells (HMSCs) were assayed by qPCR, the results do not match the results detected by MS [23]. This is a limitation of the current study.…”