Biocompatibility and biodistribution of matrix-bound nanovesicles in vitro and in vivo

Crum, Raphael J.; Capella-Monsonís, Héctor; Chang, Jordan; Dewey, Maynard M.; Kolich, Brian; Hall, Kelsey T.; Mossier, Salma O. El; Nascari, David G.; Hussey, George S.; Badylak, Stephen F.

doi:10.1016/j.actbio.2022.11.026

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…Nonetheless, conflicting results from other studies may be influenced by factors like low distribution within skeletal muscles prompted by oral EVs administration [ 12 , 13 ]. Administration routes, including intravenous (iv), oral (po), subcutaneous (sc), intranasal (in), and intramuscular (im), have substantial impacts on biological distribution [ 53 ], with intramuscular injection displaying robust and enduring accumulation at the injection site while minimizing extensive systemic dispersion [ 54 ]. Consequently, we utilized intramuscular injection into the quadriceps muscle for precise delivery of milk EVs in our study.…”

Section: Discussionmentioning

confidence: 99%

“…After intramuscular injection, EVs deposit within cells surrounding the injection site and interact with surrounding cells to exert their effects. Additionally, numerous studies indicate that intramuscular injection of EVs leads to significant signal accumulation at the injection site for a period of up to three days or even longer [ 54 ]. As such, HME, enriched with multiple amino acids, represents an ideal nutritional supplement for promoting skeletal muscle growth and repair.…”

Section: Discussionmentioning

confidence: 99%

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Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway

Meng,

Zhou,

et al. 2023

J Nanobiotechnol

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Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a “notable marker” after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway

Meng,

Zhou,

et al. 2023

J Nanobiotechnol

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“…MBVs were isolated from laboratory-produced porcine UB-ECM by enzymatic digestion and validated for size, morphology, and surface marker expression as performed and characterized in prior studies ( 18 , 20 , 26 ). Enzymatic digestion was performed using Liberase TL (highly purified collagenase I and collagenase II) in buffer [50 mM tris (pH 7.5), 5 mM CaCl 2 , and 150 mM NaCl] for 24 hours at room temperature on an orbital rocker.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies of administered MBV show their ability to down-regulate proinflammatory immune responses and improve outcomes in animal models of acute ocular injury, rheumatoid arthritis, and chronic heart transplant rejection (23)(24)(25). In addition, MBVs have been shown to have minimal systemic and immune toxicity in vivo and biodistribution to immune tissues such as the spleen through various routes of administration (26). This immunomodulatory capacity is mediated, at least in part, via mitigation of proinflammatory macrophages and promotion of an anti-inflammatory macrophage phenotype without apparent loss of immune competence.…”

Section: Introductionmentioning

confidence: 99%

Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

Crum,

Huckestien,

Dwyer

et al. 2023

Sci. Adv.

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Cytokine storm describes a life-threatening, systemic inflammatory syndrome characterized by elevated levels of proinflammatory cytokines and immune cell hyperactivation associated with multi-organ dysfunction. Matrix-bound nanovesicles (MBV) are a subclass of extracellular vesicle shown to down-regulate proinflammatory immune responses. The objective of this study was to assess the efficacy of MBV in mediating influenza-induced acute respiratory distress syndrome and cytokine storm in a murine model. Intravenous administration of MBV decreased influenza-mediated total lung inflammatory cell density, proinflammatory macrophage frequencies, and proinflammatory cytokines at 7 and 21 days following viral inoculation. MBV decreased long-lasting alveolitis and the proportion of lung undergoing inflammatory tissue repair at day 21. MBV increased the proportion of activated anti-viral CD4 + and CD8 + T cells at day 7 and memory-like CD62L + CD44 + , CD4 + , and CD8 + T cells at day 21. These results show immunomodulatory properties of MBV that may benefit the treatment of viral-mediated pulmonary inflammation with applicability to other viral diseases such as SARS-CoV-2.

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“…These contents seem to greatly contribute to the immunomodulatory potential of dECM biomaterials. In different studies, MBVs, even when isolated from different tissue sources, have shown the ability to recapitulate the immunomodulatory and regenerative potential of dECM, and have been successfully used both in vitro and in vivo for different regenerative medicine applications, suggesting their vast potential for biomedical applications [27][28][29][30][31][32][33][34]. Even though MBVs seem to be a ubiquitous component of the ECM, maintained even after the tissue decellularisation process, to date, they have only been isolated from small intestine submucosa, urinary bladder matrix, dermis, brain, oesophagus, heart, muscle, liver, ovary, pancreas, and tendons [23][24][25]35].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of Matrix-Bound Nanovesicles (MBVs) Isolated from Decellularised Bovine Pericardium: New Frontiers in Regenerative Medicine

Di Francesco,

Di Varsavia,

Casarella

et al. 2024

IJMS

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Matrix-bound nanovesicles (MBVs) are a recently discovered type of extracellular vesicles (EVs), and they are characterised by a strong adhesion to extracellular matrix structural proteins (ECM) and ECM-derived biomaterials. MBVs contain a highly bioactive and tissue-specific cargo that recapitulates the biological activity of the source ECM. The rich content of MBVs has shown to be capable of potent cell signalling and of modulating the immune system, thus the raising interest for their application in regenerative medicine. Given the tissue-specificity and the youthfulness of research on MBVs, until now they have only been isolated from a few ECM sources. Therefore, the objective of this research was to isolate and identify the presence of MBVs in decellularised bovine pericardium ECM and to characterise their protein content, which is expected to play a major role in their biological potential. The results showed that nanovesicles, corresponding to the definition of recently described MBVs, could be isolated from decellularised bovine pericardium ECM. Moreover, these MBVs were composed of numerous proteins and cytokines, thus preserving a highly potential biological effect. Overall, this research shows that bovine pericardium MBVs show a rich and tissue-specific biological potential.

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Biocompatibility and biodistribution of matrix-bound nanovesicles in vitro and in vivo

Cited by 10 publications

References 54 publications

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway

Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

Characterisation of Matrix-Bound Nanovesicles (MBVs) Isolated from Decellularised Bovine Pericardium: New Frontiers in Regenerative Medicine

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