Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection

Park, Jongmin; Lin, Hua‐Kuo; Assaker, Jean Pierre; Jeong, Sangmoo; Huang, Chen-Han; Kurdi, Ahmed T.; Lee, Kyungheon; Fraser, Kyle; Min, Changwook; Eskandari, Siawosh K.; Routray, Sujit; Tannous, Bakhos A.; Abdi, Reza; Riella, Leonardo V.; Chandraker, Anil; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho; Azzi, Jamil

doi:10.1021/acsnano.7b05083

Cited by 114 publications

(93 citation statements)

References 25 publications

(48 reference statements)

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“…Based on the assumption that the exosomes released by immune cells into urine can serve as surrogate biomarker for kidney transplant rejection, a screen was conducted to identify markers specific to the immune cell‐derived exosomes. The results show that CD3 is the most effective marker for distinguishing patients that have a high propensity to reject transplant from non‐rejection patients …”

Section: Exosome Signaling Methodsmentioning

confidence: 99%

Exosomes for Non‐Invasive Cancer Monitoring

Kalishwaralal

Kwon

Park

2018

Biotechnology Journal

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Exosomes, membrane‐bound phospholipid vesicles having diameters of 50–200 nm, are secreted by all cell types and circulate in human body fluids. These vesicles are known to carry cellular constituents that are specific to the originating cells (e.g., cytoplasmic/membrane proteins, RNA, and DNA). Thus, exosomes, which are both structurally stable and abundant, are robust indicators of cancers and, as a result, they have been utilized to monitor this disease in a manner that is less invasive than gold standard tissue biopsies. In this review, the history of exosomes and the specific biomarkers present in exosomes that enable accurate monitoring of various diseases are described. In addition, methods for analysis of exosomes and identification of biomarkers are presented with special emphasis being given to isolation and signaling strategies. Lastly, integrated, microfluidic systems developed for exosome‐based cancer diagnosis are described and future directions that research in this area will likely take are presented.

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Section: Exosome Signaling Methodsmentioning

confidence: 99%

Exosomes for Non‐Invasive Cancer Monitoring

Kalishwaralal

Kwon

Park

2018

Biotechnology Journal

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“…In particular, urinary EVs released from the epithelium of different nephron segments could serve as biomarkers of diverse pathological states and response to therapeutic agents [5]. Previous reports demonstrated that EVs derived from speci c immune cells and EVs carrying innate immune proteins can be detected in the urine after kidney transplantation [17,18]. Thus, in the present study we characterized populations of urinary EVs derived from activated immune cells in CSFs compared to NSFs (controls).…”

Section: Introductionmentioning

confidence: 90%

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

Zhang

Kumar

Jayachandran

et al. 2020

Preprint

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Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium stone formers (CSFs) compared to non-stone formers (NSFs). Methods Incident CSFs (n = 24) and age- and sex- matched NSFs (n = 21) were studied. Clinical data were abstracted and biobanked cell-free urine samples were used to quantify specific urinary EV populations. EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23)); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results The urine pH of CSFs was lower than NSFs (P < 0.05), whereas urine excretion of calcium, phosphorus, and calcium oxalate and uric acid supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive ) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion whereas excretion of EVs expressing FGF23 correlated negatively (P < 0.05) with both urinary calcium and phosphorus excretion. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation were different between CSFs and NSFs. Thus, further validation of these and other populations of urinary EVs could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

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“…The presence of intragraft infiltration of T-cells is one of the hallmarks for the diagnosis of acute cellular rejection after kidney transplantation. A recent study has shown the higher level of CD3-positive urinary exosomes in patients with acute cellular rejection that could reflect T-cell infiltration in the renal allografts (Park et al, 2017). Similarly, a subsequent proteomics study has demonstrated the increased levels of urinary exosomal tetraspanin-1 and hemopexin in patients with T-cell-mediated rejection (Lim et al, 2018).…”

Section: Kidney Transplantationmentioning

confidence: 99%