&lt;p&gt;Osteogenic Effect of tsRNA-10277-Loaded Exosome Derived from Bone Mesenchymal Stem Cells on Steroid-Induced Osteonecrosis of the Femoral Head&lt;/p&gt;

Fang, Shanhong; He, Tianmin; Jiang, Jiarun; Li, Yongfeng; Chen, Peng

doi:10.2147/dddt.s258024

Cited by 29 publications

(26 citation statements)

References 35 publications

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“…Another degenerative bone disease where exosomal tRNAs showed significant changes in levels was identified in patients suffering from steroid-induced osteonecrosis of the femoral head (SONFH). Fang et al [ 61 ] compared the expression profile of exosomal tsRNA in a small number ( n = 10) of SONFH patients with healthy controls, and further sought to characterise the effect bone marrow-derived stem cell (BMSC) exosomes had on the pathogenesis of SONFH. The authors found three exosomal tsRNAs expressed at significantly lower levels in SONFH patients, validated by qRT-PCR.…”

Section: Resultsmentioning

confidence: 99%

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Liu

Yang

Asim

et al. 2022

IJMS

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Extracellular vesicles (EVs) are important for intercellular signalling in multi-cellular organisms. However, the role of mature transfer RNAs (tRNAs) and tRNA fragments in EVs has yet to be characterised. This systematic review aimed to identify up-to-date literature on tRNAs present within human EVs and explores their potential clinical significance in health and disease. A comprehensive and systematic literature search was performed, and the study was conducted in accordance with PRISMA guidelines. Electronic databases MEDLINE and EMBASE were searched up until 1 January 2022. From 685 papers, 60 studies were identified for analysis. The majority of papers reviewed focussed on the role of EV tRNAs in cancers (31.7%), with numerous other conditions represented. Blood and cell lines were the most common EV sources, representing 85.9% of protocols used. EV isolation methods included most known methods, precipitation being the most common (49.3%). The proportion of EV tRNAs was highly variable, ranging between 0.04% to >95% depending on tissue source. EV tRNAs are present in a multitude of sources and show promise as disease markers in breast cancer, gastrointestinal cancers, and other diseases. EV tRNA research is an emerging field, with increasing numbers of papers highlighting novel methodologies for tRNA and tRNA fragment discovery.

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Section: Resultsmentioning

confidence: 99%

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Liu

Yang

Asim

et al. 2022

IJMS

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“…This potential link between secretion of exosomes containing these two RNAs by ESCC cells and increased amount of them in salivary exosomes from ESCC patients suggested that their amounts in salivary exosomes might have diagnostic and/or prognostic value. Although tsRNAs in exosomes were investigated in some published studies [ 16 , 35 – 37 ], this is the first report of salivary exosomal tsRNA as a disease biomarker.…”

Section: Discussionmentioning

confidence: 99%

A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study

et al. 2022

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Background The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC). Methods Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature. Results The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90–8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24–6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29–0.77) and PFS (HR 0.36, 95%CI 0.21–0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort. Conclusions The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy. Trial registration A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507. Registered 3 April 2016 - Retrospectively registered.

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“…Utilizing this strategy, tRNA derived small non-coding RNA-10277 i.e., tsRNA-10277 was loaded into BMSC derived exosomes. These tsRNA-10277 enriched exosomes were shown to enhance osteogenic differentiation of recipient BMSCs [61]. Overall, from the available literature it appears that tRFs are a biproduct of cellular metabolism, expelled into exosomes, which have distal gene regulatory effect.…”

Section: Trnamentioning

confidence: 97%

“…When a particular nucleic acid is overexpressed in cell either from a plasmid or due to change in cellular microenvironment, the excess nucleic acid gets routed in MVB and gets exported as exosomal cargo. To exemplify, delivery of exosomal tsRNA-10277 [61], circRNA NRIP [84] or mRNA [98] fit in this model. Induction of double stranded breaks in genomic DNA yields excess DNA fragments which gets packaged in the exosome [106].…”

Section: Cellular Abundance Induced Packaging Modelmentioning

confidence: 99%

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

Shrivastava

Morris

2021

Genes

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Exosomes are packaged with a variety of cellular cargo including RNA, DNA, lipids and proteins. For several decades now there has been ongoing debate as to what extent exosomes are the garbage bin of the cell or if these entities function as a distributer of cellular cargo which acts in a meaningful mechanistic way on target cells. Are the contents of exosomes unwanted excess cellular produce or are they selective nucleic acid packaged nanoparticles used to communicate in a paracrine fashion? Overexpressed RNAs and fragments of DNA have been shown to collect into exosomes which are jettisoned from cells in response to particular stimuli to maintain homeostasis suggesting exosomes are functional trash bins of the cell. Other studies however have deciphered selective packaging of particular nucleic acids into exosomes. Nucleic acids packaged into exosomes are increasingly reported to exert transcriptional control on recipient cells, supporting the notion that exosomes may provide a role in signaling and intracellular communication. We survey the literature and conclude that exosomes are multifunctional entities, with a plethora of roles that can each be taken advantage to functionally modulate cells. We also note that the potential utility of developing exosomes as a next generation genetic therapy may in future transform cellular therapies. We also depict three models of methodologies which can be adopted by researchers intending to package nucleic acid in exosomes for developing gene and cell therapy.

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<p>Osteogenic Effect of tsRNA-10277-Loaded Exosome Derived from Bone Mesenchymal Stem Cells on Steroid-Induced Osteonecrosis of the Femoral Head</p>

Cited by 29 publications

References 35 publications

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

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