Renal Endothelial Cell‐Targeted Extracellular Vesicles Protect the Kidney from Ischemic Injury

Abstract

Endothelial cell injury plays a critical part in ischemic acute kidney injury (AKI) and participates in the progression of AKI. Targeting renal endothelial cell therapy may ameliorate vascular injury and further improve the prognosis of ischemic AKI. Here, P‐selectin as a biomarker of ischemic AKI in endothelial cells is identified and P‐selectin binding peptide (PBP)‐engineered extracellular vesicles (PBP‐EVs) with imaging and therapeutic functions are developed. The results show that PBP‐EVs exhibit a selective targeting tendency to injured kidneys, while providing spatiotemporal information for the early diagnosis of AKI by quantifying the expression of P‐selectin in the kidneys by molecular imaging. Meanwhile, PBP‐EVs reveal superior nephroprotective functions in the promotion of renal repair and inhibition of fibrosis by alleviating inflammatory infiltration, improving reparative angiogenesis, and ameliorating maladaptive repair of the renal parenchyma. In conclusion, PBP‐EVs, as an ischemic AKI theranostic system that is designed in this study, provide a spatiotemporal diagnosis in the early stages of AKI to help guide personalized therapy and exhibit superior nephroprotective effects, offering proof‐of‐concept data to design EV‐based theranostic strategies to promote renal recovery and further improve long‐term outcomes following AKI.

Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation

“…Both primary and preclinical applications of MSC-based therapy have powerfully attracted attention for the development of ARDS treatments and other lung disorders [ 11 , 46 ]. By transferring several bioactive molecules, MSCs play a crucial role in physiological and pathological conditions [ 32 , 47 ]. The interaction between MSCs and target cells is critical for their MSC functions [ 38 , 48 , 49 ].…”

Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy

“…Subsequently, 200 μL of 1 mg/mL NO prodrug, MGP, was administered via tail vein injection and then once for the other day until the end of the experiment. To monitor angiogenesis in real time in vivo , a C57BL/6 albino and outbred (Nu/Nu) background Vegfr2-luciferase transgenic mice (10 weeks old, female) were used to establish an AKI model induced by I/R injury (29). This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.…”

A quantitative review of nanotechnology‐based therapeutics for kidney diseases

“…Similar to synthetic NPs, specific ligands can be incorporated into the EV membrane to enhance kidney targeting. Zhang et al previously demonstrated that modification with P-selectin binding peptide (CDAEWVDVS) onto human placental MSC-derived EVs targeting endothelial cells improved the kidney-to-liver EV binding ratio from 0.3 to 0.7 in mice with renal ischemia-reperfusion injury (K. Zhang et al, 2023). Similarly, the incorporation of KIM-1 specific binding peptide (LTHVVWL) into the membrane of red blood cell-derived EVs raised the kidney-to-liver binding ratio from 0.02 to 0.1 in mice with renal ischemia-reperfusion injury without causing organ toxicity (Tang et al, 2021).…”