Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials

Hussey, George S.; Molina, Catalina Pineda; Cramer, Madeline C.; Tyurina, Yulia Y.; Tyurin, Vladimir A.; Lee, Yoojin C.; El-Mossier, Salma O.; Murdock, Mark H.; Timashev, P. S.; Kagan, Valerian E.; Badylak, Stephen F.

doi:10.1126/sciadv.aay4361

Cited by 63 publications

(73 citation statements)

References 49 publications

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“…Phospholipids involved in signalling pathways crucial for cellular fate. Lipidomics is an essential tool for tissue repair and remodelling 258 Initial tissue and substrate characterisation informs material design and optimization to produce a device with high fidelity to natural tissue modifications and biological activity …”

Section: Final Characterisation To Investigate Retained Activitymentioning

confidence: 99%

“… 256 , 257 Liquid chromatography-mass spectrometry (LC-MS) based lipidomic and redox lipidomic tools can be utilised to identify tissue response and biological activity of the biomaterial. 258 Effects of lipidome profile of ECM-derived biomaterials are unknown and needed to be further investigated. Transcriptomic analyses can be performed in order to understand cell–biomaterial interactions.…”

Section: Final Characterisation To Investigate Retained Activitymentioning

confidence: 99%

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Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

Joyce

Fabra

Bozkurt

et al. 2021

Sig Transduct Target Ther

149

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Biomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.

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Section: Final Characterisation To Investigate Retained Activitymentioning

confidence: 99%

Section: Final Characterisation To Investigate Retained Activitymentioning

confidence: 99%

Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

Joyce

Fabra

Bozkurt

et al. 2021

Sig Transduct Target Ther

149

View full text Add to dashboard Cite

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“…Omics technologies are continuing to uncover and describe distinct EV subtypes in specialized biological contexts. Stephen Badylak's group at Pittsburg has provided numerous accounts of matrix-bound nanovesicles, which are solid-phase EVs deposited into the extracellular matrix rather than into a liquid-phase (Huleihel et al, 2016 ; Hussey et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…In bone and associated connective tissues, EVs are crystal nucleation sites associated with both facilitation (Anderson, 1969 ; Ali et al, 1970 ; Hasegawa et al, 2017 ) and inhibition (Li et al, 2019 ) of mineralization. Solid-phase EVs, which are often called matrix vesicles, have also been located in extracellular matrices more generally, although they have an indeterminate biological role (Huleihel et al, 2016 ; Hussey et al, 2020 ). During exercise, organism-wide signaling cascades involved with the physical stress response are mediated by a variety of myokines and regulatory RNAs.…”

Section: Extracellular Vesicle Physiology and Biomedical Relevancementioning

confidence: 99%

Characterizing Extracellular Vesicles and Their Diverse RNA Contents

2020

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Cells release nanometer-scale, lipid bilayer-enclosed biomolecular packages (extracellular vesicles; EVs) into their surrounding environment. EVs are hypothesized to be intercellular communication agents that regulate physiological states by transporting biomolecules between near and distant cells. The research community has consistently advocated for the importance of RNA contents in EVs by demonstrating that: (1) EV-related RNA contents can be detected in a liquid biopsy, (2) disease states significantly alter EV-related RNA contents, and (3) sensitive and specific liquid biopsies can be implemented in precision medicine settings by measuring EV-derived RNA contents. Furthermore, EVs have medical potential beyond diagnostics. Both natural and engineered EVs are being investigated for therapeutic applications such as regenerative medicine and as drug delivery agents. This review focuses specifically on EV characterization, analysis of their RNA content, and their functional implications. The NIH extracellular RNA communication (ERC) program has catapulted human EV research from an RNA profiling standpoint by standardizing the pipeline for working with EV transcriptomics data, and creating a centralized database for the scientific community. There are currently thousands of RNA-sequencing profiles hosted on the Extracellular RNA Atlas alone (Murillo et al., 2019 ), encompassing a variety of human biofluid types and health conditions. While a number of significant discoveries have been made through these studies individually, integrative analyses of these data have thus far been limited. A primary focus of the ERC program over the next five years is to bring higher resolution tools to the EV research community so that investigators can isolate and analyze EV sub-populations, and ultimately single EVs sourced from discrete cell types, tissues, and complex biofluids. Higher resolution techniques will be essential for evaluating the roles of circulating EVs at a level which impacts clinical decision making. We expect that advances in microfluidic technologies will drive near-term innovation and discoveries about the diverse RNA contents of EVs. Long-term translation of EV-based RNA profiling into a mainstay medical diagnostic tool will depend upon identifying robust patterns of circulating genetic material that correlate with a change in health status.

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“…Some studies in literature are focused on multi-omics integration, mainly based on proteomics and miRNAs [ 26 ]. However, few studies are focused on lipidomic and miRNAs integration, which allow us to identify different biological activities involved in cell communication [ 27 ]. In general, the integration of omics results (lipidomics, metabolomics, proteomics, epigenomics) helps to give a global image of the mechanisms involved in complex diseases [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenomics and Lipidomics Integration in Alzheimer Disease: Pathways Involved in Early Stages

et al. 2021

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Background: Alzheimer Disease (AD) is the most prevalent dementia. However, the physiopathological mechanisms involved in its development are unclear. In this sense, a multi-omics approach could provide some progress. Methods: Epigenomic and lipidomic analysis were carried out in plasma samples from patients with mild cognitive impairment (MCI) due to AD (n = 22), and healthy controls (n = 5). Then, omics integration between microRNAs (miRNAs) and lipids was performed by Sparse Partial Least Squares (s-PLS) regression and target genes for the selected miRNAs were identified. Results: 25 miRNAs and 25 lipids with higher loadings in the sPLS regression were selected. Lipids from phosphatidylethanolamines (PE), lysophosphatidylcholines (LPC), ceramides, phosphatidylcholines (PC), triglycerides (TG) and several long chain fatty acids families were identified as differentially expressed in AD. Among them, several fatty acids showed strong positive correlations with miRNAs studied. In fact, these miRNAs regulated genes implied in fatty acids metabolism, as elongation of very long-chain fatty acids (ELOVL), and fatty acid desaturases (FADs). Conclusions: The lipidomic–epigenomic integration showed that several lipids and miRNAs were differentially expressed in AD, being the fatty acids mechanisms potentially involved in the disease development. However, further work about targeted analysis should be carried out in a larger cohort, in order to validate these preliminary results and study the proposed pathways in detail.

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Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials

Cited by 63 publications

References 49 publications

Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

Characterizing Extracellular Vesicles and Their Diverse RNA Contents

Epigenomics and Lipidomics Integration in Alzheimer Disease: Pathways Involved in Early Stages

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