Matrix-Bound Nanovesicles: The Effects of Isolation Method upon Yield, Purity, and Function
Open accessAbstract
Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) raises questions regarding their biologic functions and their potential theranostic application. Unlike liquid-phase extracellular vesicles (e.g., exosomes), MBV are tightly bound to the ECM, which makes their isolation and harvesting more challenging. The indiscriminate use of different methods to harvest MBV can alter or disrupt their structural and/or functional integrity. The objective of the present study was to compare the effect of various MBV harvesting methods upon yield, purity, and biologic activity. Combinations of four methods to solubilize the ECM (collagenase [COL], liberase [LIB], or proteinase K [PK] and nonenzymatic elution with potassium chloride) and four isolation methods (ultracentrifugation, ultrafiltration [UF], density barrier, and size exclusion chromatography [SEC]) were used to isolate MBV from urinary bladder-derived ECM. All combinations of solubilization and isolation methods allowed for the harvesting of MBV, however, distinct differences were noted. The highest yield, purity, cellular uptake, and biologic activity were seen with MBV isolated by a combination of liberase or collagenase followed by SEC. The combination of proteinase K and UF was shown to have detrimental effects on bioactivity. The results show the importance of selecting appropriate MBV harvesting methods for the characterization and evaluation of MBV and for analysis of their potential theranostic application. Impact statement: Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) has raised questions regarding their biologic functions and their potential theranostic application. This study demonstrates that the harvesting methods used can result in samples with physical and biochemical properties that are unique to the isolation and solubilization methods used. Consequently, developing harvesting methods that minimize sample contamination with ECM remnants and/or solubilization agents will be essential in determining the theranostic potential of MBV in future studies.
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Degradation of ECM biomaterials upon implantation is necessary to promote their pro-regenerative effect.
“MBV independence at promoting a pro-remodeling response [163,166] further proves the necessity for the degradation of ECM biomaterials upon implantation to promote their pro-regenerative effect.”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [166]
Independently of the methodology used to decellularize the ECM, all decellularized tissue has shown MBV to date.
“Interestingly, independently of the methodology used to decellularize the ECM, all decellularized tissue has shown MBV to date, proving the resilience of the MBV and the tight ECM-MBV relationship [163,166,167].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [166]
Cites
1 retracted
Cheng, Z., Dai, L., Wang, X., Jia, L., Jing, X., Li, P., Liu, M., Wang, H., & An, L. K. (2017) · Oncotarget · doi:10.18632/oncotarget.17933 · Cited by 28 · see citing works
RetractedThéry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin‐Smith, G. K., et al. (2018) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2018.1535750 · Cited by 11,099 · see citing works
Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606 · see citing works
Shedding light on the cell biology of extracellular vesicles
van Niel, G., D'Angelo, G., & Raposo, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.125 · Cited by 8,369 · see citing works
Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
Colombo, M., Raposo, G., & Théry, C. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122326 · Cited by 6,186 · see citing works
Biological properties of extracellular vesicles and their physiological functions
Yáñez‐Mó, M., Siljander, P. R. ‐., Andreu, Z., Bedina Zavec, A., Borràs, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27066 · Cited by 5,926 · see citing works
Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
Théry, C., Amigorena, S., Raposo, G., & Clayton, A. (2006) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0322s30 · Cited by 5,766 · see citing works
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991 · see citing works
Self-citationThe Extracellular Matrix: Not Just Pretty Fibrils
Hynes, R. O. (2009) · Science · doi:10.1126/science.1176009 · Cited by 3,527 · see citing works
Extracellular vesicles: biology and emerging therapeutic opportunities
EL Andaloussi, S., Mäger, I., Breakefield, X. O., & Wood, M. J. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3978 · Cited by 3,254 · see citing works
Identification and proteomic profiling of exosomes in human urine
Pisitkun, T., Shen, R., & Knepper, M. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403453101 · Cited by 2,162 · see citing works
Filipe, V., Hawe, A., & Jiskoot, W. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0073-2 · Cited by 1,885 · see citing works
CellProfiler 3.0: Next-generation image processing for biology
McQuin, C., Goodman, A., Chernyshev, V. S., Kamentsky, L. D., Cimini, B. A., Karhohs, K. W., Doan, M., Ding, L., Rafelski, S. M., Thirstrup, D. J., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005970 · Cited by 1,835 · see citing works
Concise review: MSC-derived exosomes for cell-free therapy
Phinney, D. G., & Pittenger, M. F. (2017) · Stem Cells · doi:10.1002/stem.2575 · Cited by 1,834 · see citing works
Abels, E. R., & Breakefield, X. O. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0366-z · Cited by 1,685 · see citing works
Exosomal-like vesicles are present in human blood plasma
Caby, M.-P., Lankar, D., Vincendeau-Scherrer, C., Raposo, G., & Bonnerot, C. (2005) · International Immunology · doi:10.1093/intimm/dxh267 · Cited by 1,348 · see citing works
Exosome Theranostics: Biology and Translational Medicine
He, C., Zheng, S., Luo, Y., & Wang, B. (2017) · Theranostics · doi:10.7150/thno.21945 · Cited by 1,259 · see citing works
Gurunathan, S., Kang, M.-H., Jeyaraj, M., Qasim, M., & Kim, J. (2019) · Cells · doi:10.3390/cells8040307 · Cited by 1,135 · see citing works
VESICLES ASSOCIATED WITH CALCIFICATION IN THE MATRIX OF EPIPHYSEAL CARTILAGE
Anderson, H. C. (1969) · The Journal of Cell Biology · doi:10.1083/jcb.41.1.59 · Cited by 1,046 · see citing works
Exosomes: Therapy delivery tools and biomarkers of diseases
Barile, L., & Vassalli, G. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.020 · Cited by 1,038 · see citing works
Webber, J., & Clayton, A. (2013) · Journal of Extracellular Vesicles · doi:10.3402/jev.v2i0.19861 · Cited by 817 · see citing works
Brown, B. N., Londono, R., Tottey, S., Zhang, L., Kukla, K. A., Wolf, M. T., Daly, K. A., Reing, J. E., & Badylak, S. F. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.11.031 · Cited by 745 · see citing works
Self-citationBaranyai, T., Herczeg, K., Onódi, Z., Voszka, I., Módos, K., Marton, N., Nagy, G., Mäger, I., Wood, M. J. A., Andaloussi, S. E., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0145686 · Cited by 677 · see citing works
Proteinase K from Tritirachium album Limber
Ebeling, W., Hennrich, N., Klockow, M., Metz, H., Orth, H., & Lang, H. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03671.x · Cited by 639 · see citing works
Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes
Taylor, D. D., & Shah, S. (2015) · Methods · doi:10.1016/j.ymeth.2015.02.019 · Cited by 634 · see citing works
Kalra, H., Adda, C. G., Liem, M. K., Ang, C., Mechler, Á., Simpson, R. J., Hulett, M. D., & Mathivanan, S. (2013) · PROTEOMICS · doi:10.1002/pmic.201300282 · Cited by 625 · see citing works
Essandoh, K., Li, Y., Huo, J., & Fan, G. (2016) · Shock · doi:10.1097/shk.0000000000000604 · Cited by 603 · see citing works
Isolation and Characterization of Calcifying Matrix Vesicles from Epiphyseal Cartilage
Ali, S. Y., Sajdera, S. W., & Anderson, H. C. (1970) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.67.3.1513 · Cited by 575 · see citing works
Haraszti, R. A., Miller, R., Stoppato, M., Sere, Y. Y., Coles, A., Didiot, M.-C., Wollacott, R., Sapp, E., Dubuke, M. L., Li, X., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.09.015 · Cited by 567 · see citing works
Busatto, S., Vilanilam, G. K., Ticer, T. D., Lin, W., Dickson, D. W., Shapiro, S. A., Bergese, P., & Wolfram, J. (2018) · Cells · doi:10.3390/cells7120273 · Cited by 538 · see citing works
Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions
György, B., Hung, M. E., Breakefield, X. O., & Leonard, J. N. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124630 · Cited by 512 · see citing works
Cvjetkovic, A., Lötvall, J. O., & Lässer, C. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.23111 · Cited by 489 · see citing works
Matrix-bound nanovesicles within ECM bioscaffolds
Huleihel, L., Hussey, G. S., Naranjo, J. D., Zhang, L., Dziki, J. L., Turner, N. J., Stolz, D. B., & Badylak, S. F. (2016) · Science Advances · doi:10.1126/sciadv.1600502 · Cited by 387 · see citing works
Self-citationExosome isolation from distinct biofluids using precipitation and column-based approaches
Martins, T. S., Catita, J. A. M., Rosa, I. M., Silva, O. A. B. D. C. E., & Henriques, A. G. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198820 · Cited by 369 · see citing works
Comparison of serum exosome isolation methods for microRNA profiling
Rekker, K., Saare, M., Roost, A. M., Kubo, A., Zarovni, N., Chiesi, A., Salumets, A., & Peters, M. (2013) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2013.10.020 · Cited by 327 · see citing works
Improved Human Islet Isolation Using a New Enzyme Blend, Liberase
Linetsky, E., Bottino, R., Lehmann, R., Alejandro, R., Inverardi, L., & Ricordi, C. (1997) · Diabetes · doi:10.2337/diab.46.7.1120 · Cited by 309 · see citing works
Mase, V. J., Hsu, J. R., Wolf, S. E., Wenke, J. C., Baer, D. G., Owens, J. G., Badylak, S. F., & Walters, J. (2010) · Orthopedics · doi:10.3928/01477447-20100526-24 · Cited by 291 · see citing works
Self-citationThe impact of detergents on the tissue decellularization process: A ToF-SIMS study
White, L. J., Taylor, A. J., Faulk, D. M., Keane, T. J., Saldin, L. T., Reing, J. E., Swinehart, I. T., Turner, N. J., Ratner, B. D., & Badylak, S. F. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.12.033 · Cited by 268 · see citing works
Self-citationProteomic Analysis of Two Types of Exosomes in Human Whole Saliva
Ogawa, Y., Miura, Y., Harazono, A., Kanai‐Azuma, M., Akimoto, Y., Kawakami, H., Yamaguchi, T., Toda, T., Endo, T., Tsubuki, M., et al. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.13 · Cited by 262 · see citing works
Gupta, S., Rawat, S. J., Arora, V., Kottarath, S. K., Dinda, A. K., Vaishnav, P. K., Nayak, B., & Mohanty, S. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0923-0 · Cited by 261 · see citing works
Impact of Biofluid Viscosity on Size and Sedimentation Efficiency of the Isolated Microvesicles
Momen‐Heravi, F., Balaj, L., Alian, S., Trachtenberg, A. J., Hochberg, F. H., Skog, J., & Kuo, W. P. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00162 · Cited by 258 · see citing works
An, M., Wu, J., Zhu, J., & Lubman, D. M. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00479 · Cited by 219 · see citing works
Size‐exclusion chromatography‐based enrichment of extracellular vesicles from urine samples
Lozano‐Ramos, I., Bancu, I., Oliveira‐Tercero, A., Armengol, M. P., Menezes‐Neto, A., Portillo, H. A. D., Lauzurica, R., & Borràs, F. E. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27369 · Cited by 215 · see citing works
Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis
Swinehart, I. T., & Badylak, S. F. (2015) · Developmental Dynamics · doi:10.1002/dvdy.24379 · Cited by 208 · see citing works
Self-citationIsolation of Extracellular Vesicles by Ultracentrifugation
Momen‐Heravi, F. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7253-1_3 · Cited by 197 · see citing works
Heat shock protein-containing exosomes in mid-trimester amniotic fluids
Asea, A. A. A., Jean-Pierre, C., Kaur, P., Rao, P., Linhares, I. M., Skupski, D. W., & Witkin, S. S. (2008) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2008.06.001 · Cited by 196 · see citing works
Gheinani, A. H., Vögeli, M., Baumgartner, U., Vassella, E., Draeger, A., Burkhard, F. C., & Monastyrskaya, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-22142-x · Cited by 195 · see citing works
Expression profiles of miRNAs in polarized macrophages
Zhang, Y., Zhang, M., Zhong, M., Suo, Q., & Lv, K. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2013.1260 · Cited by 192 · see citing works
Surface characterization of extracellular matrix scaffolds
Brown, B. N., Barnes, C. A., Kasick, R. T., Michel, R., Gilbert, T. W., Beer–Stolz, D., Castner, D. G., Ratner, B. D., & Badylak, S. F. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.061 · Cited by 180 · see citing works
Self-citationAgrawal, V., Tottey, S., Johnson, S. A., Freund, J. M., Siu, B. F., & Badylak, S. F. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0036 · Cited by 180 · see citing works
Self-citationRosario, D. J., Reilly, G. C., Salah, E., Glover, M., Bullock, A. J., & MacNeil, S. (2008) · Regenerative Medicine · doi:10.2217/17460751.3.2.145 · Cited by 174 · see citing works
Extracellular vesicles — new tool for joint repair and regeneration
Malda, J., Boere, J., van de Lest, C. H. A., van Weeren, P. R., & Wauben, M. H. M. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.170 · Cited by 167 · see citing works
Zhang, J., Hu, Z. Q., Turner, N. J., Teng, S. F., Cheng, W. Y., Zhou, H. Y., Zhang, L., Hu, H. W., Wang, Q., & Badylak, S. F. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.02.040 · Cited by 141 · see citing works
Self-citationBiogenesis and Functions of Exosomes and Extracellular Vesicles
Dreyer, F. S., & Baur, A. S. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3753-0_15 · Cited by 135 · see citing works
Sicari, B. M., Johnson, S., Siu, B., Crapo, P. M., Daly, K. A., Jiang, H.-B., Medberry, C. J., Tottey, S., Turner, N., & Badylak, S. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.04.017 · Cited by 134 · see citing works
Self-citationA method for the isolation and enrichment of purified bovine milk exosomes
Vaswani, K., Koh, Y. Q., Almughlliq, F. B., Peiris, H. N., & Mitchell, M. D. (2017) · Reproductive Biology · doi:10.1016/j.repbio.2017.09.007 · Cited by 128 · see citing works
Brennan-Pierce, E. P., Tang, X., Stewart‐Akers, A. M., Gudas, L. J., & Badylak, S. F. (2008) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.123 · Cited by 125 · see citing works
Self-citationMatrix-bound nanovesicles recapitulate extracellular matrix effects on macrophage phenotype
Huleihel, L., Bartolacci, J. G., Dziki, J. L., Vorobyov, T., Arnold, B., Scarritt, M. E., Pineda Molina, C., LoPresti, S. T., Brown, B. N., Naranjo, J. D., et al. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0102 · Cited by 116 · see citing works
Self-citationHussey, G. S., Molina, C. P., Cramer, M. C., Tyurina, Y. Y., Tyurin, V. A., Lee, Y. C., El-Mossier, S. O., Murdock, M. H., Timashev, P. S., Kagan, V. E., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay4361 · Cited by 109 · see citing works
Self-citationShin, S., Han, D., Park, M., Mun, J. Y., Choi, J. H., Chun, H., Kim, S., & Hong, J. W. (2017) · Scientific Reports · doi:10.1038/s41598-017-08826-w · Cited by 91 · see citing works
Terrasini, N., & Lionetti, V. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002328 · Cited by 90 · see citing works
MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte autophagy
Higashi, K., Yamada, Y., Minatoguchi, S., Baba, S., Iwasa, M., Kanamori, H., Kawasaki, M., Nishigaki, K., Takemura, G., Kumazaki, M., et al. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00709.2014 · Cited by 82 · see citing works
Agrawal, V., Kelly, J., Tottey, S., Daly, K. A., Johnson, S. A., Siu, B. F., Reing, J. E., & Badylak, S. F. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0257 · Cited by 81 · see citing works
Self-citationProfiling microRNA expression during fracture healing
Waki, T., Lee, S. Y., Niikura, T., Iwakura, T., Dogaki, Y., Okumachi, E., Oe, K., Kuroda, R., & Kurosaka, M. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-0931-0 · Cited by 79 · see citing works
Calcification of isolated matrix vesicles and reconstituted vesicles from fetal bovine cartilage.
Hsu, H. H. T., & Anderson, H. C. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.8.3805 · Cited by 76 · see citing works
van der Merwe, Y., Faust, A. E., Sakalli, E. T., Westrick, C. C., Hussey, G. S., Chan, K. C., Conner, I. P., Fu, V. L. N., Badylak, S. F., & Steketee, M. B. (2019) · Scientific Reports · doi:10.1038/s41598-019-39861-4 · Cited by 70 · see citing works
Self-citationExtracellular Matrix Bioscaffolds for Building Gastrointestinal Tissue
Hussey, G. S., Cramer, M. C., & Badylak, S. F. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.09.004 · Cited by 69 · see citing works
Self-citationClèries, R., Gálvez, J., Espino‐Guarch, M., Ribes, J., Nunes, V., & de Heredia, M. L. (2012) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2011.12.012 · Cited by 66 · see citing works
Protein-Protein Interactions in Salt Solutions
Zhang, J. (2012) · IntechOpen eBooks · doi:10.5772/38056 · Cited by 65 · see citing works
Quiroz, J. F. D., Tsai, E. C., Coyle, M. J., Sehm, T., & Echeverri, K. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014837 · Cited by 65 · see citing works
Bab, I., Mühlrád, A., & Sela, J. (1979) · Cell and Tissue Research · doi:10.1007/bf00239215 · Cited by 51 · see citing works
Faust, A. E., Kandakatla, A., van der Merwe, Y., Ren, T., Huleihel, L., Hussey, G. S., Naranjo, J. D., Johnson, S. A., Badylak, S. F., & Steketee, M. B. (2017) · Journal of Biomaterials Applications · doi:10.1177/0885328217698062 · Cited by 50 · see citing works
Self-citationCryptic Peptides from Collagen: A Critical Review
Banerjee, P., & Shanthi, C. (2016) · Protein and Peptide Letters · doi:10.2174/0929866522666160512151313 · Cited by 41 · see citing works
Probing the mechanisms of extracellular vesicle biogenesis and function in cancer
Latifkar, A., Cerione, R. A., & Antonyak, M. A. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180523 · Cited by 37 · see citing works
Quesenberry, P. J., Aliotta, J. M., Camussi, G., Abdel‐Mageed, A. B., Wen, S., Goldberg, L. R., Zhang, H., Tetta, C., Franklin, J. L., Coffey, R. J., et al. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27575 · Cited by 36 · see citing works
Sela, J., & Bab, I. (1979) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf01102736 · Cited by 36 · see citing works
Exosomes: A Cancer Theranostics Road Map
Panagiotara, A., Markou, A. N., Lianidou, E. S., Patrinos, G. P., & Κάτσιλα, Θ. (2017) · Public Health Genomics · doi:10.1159/000478253 · Cited by 33 · see citing works
Isolation of Biologically Active Exosomes from Plasma of Patients with Cancer
Hong, C., Ludwig, S., & Whiteside, T. L. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7142-8_16 · Cited by 30 · see citing works
The role of matrix vesicles in calcification
Dereszewski, G. N., & Howell, D. S. (1978) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(78)90147-0 · Cited by 27 · see citing works
Landis, W. J., Pains, M. C., Hodgens, K. J., & Glimcher, M. J. (1986) · Journal of Ultrastructure and Molecular Structure Research · doi:10.1016/0889-1605(86)90037-6 · Cited by 26 · see citing works
Occurrence of actin-like protein in extracellular matrix vesicles
Mühlrád, A., Bab, I., Deutsch, D., & Sela, J. (1982) · Calcified Tissue International · doi:10.1007/bf02411271 · Cited by 24 · see citing works
Methods to Enrich Exosomes from Conditioned Media and Biological Fluids
Sharma, S., Scholz‐Romero, K., Rice, G. E., & Salomón, C. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7498-6_8 · Cited by 21 · see citing works
Whole rat stomach decellularisation using a detergent-enzymatic protocol
Zambaiti, E., Scottoni, F., Rizzi, E., Russo, S., Deguchi, K., Eaton, S. D., Pellegata, A. F., & Coppi, P. D. (2018) · Pediatric Surgery International · doi:10.1007/s00383-018-4372-8 · Cited by 16 · see citing works
Patterns of matrix vesicle calcification in 0steomalacia of gyro mice
Sela, J., Bab, I., & Deol, M. S. (1982) · Metabolic Bone Disease and Related Research · doi:10.1016/0221-8747(82)90026-1 · Cited by 12 · see citing works
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Popova, N. V., & Jücker, M. (2022) · Cancers · doi:10.3390/cancers14010238 · Cited by 277 · see citing works
Capella-Monsonís, H., Crum, R. J., Hussey, G. S., & Badylak, S. F. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115347 · Cited by 84 · see citing works
Self-citationCrum, R. J., Hall, K., Molina, C. P., Hussey, G. S., Graham, E., Li, H., & Badylak, S. F. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00208-9 · Cited by 50 · see citing works
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Crum, R. J., Capella-Monsonís, H., Chang, J., Dewey, M. J., Kolich, B. D., Hall, K. T., El-Mossier, S. O., Nascari, D. G., Hussey, G. S., & Badylak, S. F. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.11.026 · Cited by 42 · see citing works
Self-citationDede, E. Ç., Bozbeyoglu, N., Gürsel, İ., Korkusuz, F., Bakan, F., & Korkusuz, P. (2023) · PLoS ONE · doi:10.1371/journal.pone.0282238 · Cited by 41 · see citing works
Elnawam, H., Abdelmougod, M., Mobarak, A. M., Hussein, M., Aboualmakarem, H., Girgis, M., & Backly, R. M. E. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.837639 · Cited by 36 · see citing works
Marzano, M., Bou-Dargham, M. J., Cone, A. S., York, S. B., Helsper, S., Grant, S. C., Meckes, D. G., Sang, Q. A., & Li, Y. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01286 · Cited by 33 · see citing works
Matrix Bound Nanovesicles Have Tissue-Specific Characteristics That Suggest a Regulatory Role
Turner, N. J., Quijano, L. M., Hussey, G. S., Jiang, P., & Badylak, S. F. (2022) · Tissue Engineering Part A · doi:10.1089/ten.tea.2022.0091 · Cited by 32 · see citing works
Self-citationMuok, L., Sun, L. J., Esmonde, C., Worden, H., Vied, C., Duke, L. C., Ma, S., Zeng, O. Z., Driscoll, T. P., Jung, S., et al. (2024) · Journal of Extracellular Biology · doi:10.1002/jex2.133 · Cited by 31 · see citing works
Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles
Crum, R. J., Huckestien, B. R., Dwyer, G., Mathews, L., Nascari, D. G., Hussey, G. S., Turnquist, H. R., Alcorn, J. F., & Badylak, S. F. (2023) · Science Advances · doi:10.1126/sciadv.adf9016 · Cited by 25 · see citing works
Self-citationBartolacci, J., Behun, M., Warunek, J., Li, T., Sahu, A., Dwyer, G., Lucas, A., Rong, J., Ambrósio, F., Turnquist, H. R., et al. (2024) · npj Regenerative Medicine · doi:10.1038/s41536-024-00346-2 · Cited by 17 · see citing works
Self-citationMatrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis
Liao, R., Dewey, M. J., Rong, J., Johnson, S. A., D’Angelo, W. A., Hussey, G. S., & Badylak, S. F. (2024) · Science Advances · doi:10.1126/sciadv.adn1852 · Cited by 20 · see citing works
Self-citationExtracellular Vesicles for Regenerative Medicine Applications
Crum, R. J., Capella‐Monsonís, H., Badylak, S. F., & Hussey, G. S. (2022) · Applied Sciences · doi:10.3390/app12157472 · Cited by 17 · see citing works
Self-citationLiu, C., Chen, X., Ene, J., Esmonde, C., Kanekiyo, T., Zeng, C., Sun, L. J., & Li, Y. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c22692 · Cited by 16 · see citing works
Liu, C., Chen, X., Liu, Y., Sun, L. J., Yu, Z., Ren, Y., Zeng, C., & Li, Y. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301112 · Cited by 16 · see citing works
Interfacing extracellular vesicles with bioengineered materials for regenerative medicine
Atanasov, K. S., Bagur-Cardona, S., Chiera, S., Capella‐Monsonís, H., & Gómez‐Florit, M. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.10.022 · Cited by 14 · see citing works
Francesco, D. D., Varsavia, C. D., Casarella, S., Donetti, E., Manfredi, M., Mantovani, D., & Boccafoschi, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020740 · Cited by 12 · see citing works
Extracellular vesicles: unlocking therapeutic potential in regenerative medicine
Samadi, P., Sheykhhasan, M., Mokhtari, K., Yang, P., Maghool, F., & Kalhor, N. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-23891-8.00003-2 · Cited by 11 · see citing works
Kobayashi, M., Negishi, J., Ishida, N., Hashimoto, Y., Sasaki, Y., Akiyoshi, K., Kimura, T., & Kishida, A. (2024) · Science and Technology of Advanced Materials · doi:10.1080/14686996.2024.2404380 · Cited by 10 · see citing works
Kobayashi, M., Ishida, N., Hashimoto, Y., Negishi, J., Saga, H., Sasaki, Y., Akiyoshi, K., Kimura, T., & Kishida, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168868 · Cited by 10 · see citing works
Park, H., Morales, K. J. D. J., Bheri, S., Kassouf, B. P., & Davis, M. E. (2021) · Stem Cells · doi:10.1002/stem.3445 · Cited by 9 · see citing works
Cramer, M. C., D’Angelo, W., Dewey, M. J., Manuel, A. M., Mullett, S. J., Wendell, S. G., Napierala, D., Jiang, P., & Badylak, S. F. (2022) · Journal of Immunology and Regenerative Medicine · doi:10.1016/j.regen.2022.100066 · Cited by 9 · see citing works
Self-citationElectrospun meshes for abdominal wall hernia repair: Potential and challenges
Liu, Z., Liu, L., Liu, J., Wu, J., Tang, R., & Wolfram, J. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.01.028 · Cited by 7 · see citing works
Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review
Romero, D. J., Hussey, G., & Capella-Monsonís, H. (2025) · Biologics · doi:10.3390/biologics5030028 · Cited by 7 · see citing works
“MBV independence at promoting a pro-remodeling response [163,166] further proves the necessity for the degradation of ECM biomaterials upon implantation to promote their pro-regenerative effect.”
From isolation to detection, advancing insights into endothelial matrix-bound vesicles
Ayus-Martinez, S., Meza-Morales, W., Jimenez-Osorio, J., Buendia-Otero, M., López, L., Cunci, L., Freytes, D. O., & Mora‐Navarro, C. (2024) · Extracellular Vesicle · doi:10.1016/j.vesic.2024.100060 · Cited by 6 · see citing works
Chen, Z.-H., Hu, Y., Yue, X.-B., Zhao, K., Yang, H., Liu, Z.-G., Xu, R., & Lü, W. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102355 · Cited by 5 · see citing works
Immuno‐Regulation of Brain Region‐Specific Organoids Containing Isogenic Microglia‐Like Cells
Liu, C., Ene, J., Lü, W., Syed, F., Sun, L. J., Raulin, A., Ren, Y., Wang, X. S., Kanekiyo, T., & Li, Y. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503579 · Cited by 5 · see citing works
Liu, B., Zhang, X., Wei, N., Wu, X., Yuan, P., Zeng, T., Liang, L., Zhang, H., & Wu, W. T. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123769 · Cited by 3 · see citing works
Migrasomes, Matrix‐Bound Nanovesicles, and More: Messengers in the Matrix
Kolesov, A. V., Reitz, N., Dewey, M. J., & Hisey, C. L. (2025) · PROTEOMICS · doi:10.1002/pmic.70056 · Cited by 3 · see citing works
Piening, L. M., Wolfe, P. N., Shepard, D., Fortier, L. A., & Baria, M. R. (2025) · The American Journal of Sports Medicine · doi:10.1177/03635465251391709 · Cited by 2 · see citing works
Matrix-bound nanovesicles as epigenetic modulators of myeloid cells
Capella‐Monsonís, H., Rong, J., Chirravuri, B., D’Angelo, W., Turnquist, H. R., Hussey, G. S., & Badylak, S. F. (2026) · Science Advances · doi:10.1126/sciadv.adx9159 · Cited by 2 · see citing works
Self-citationMatrix bound nanovesicles: A great promise for TERM in less than a decade of research
Francesco, D. D., Mantovani, D., Hussey, G. S., & Boccafoschi, F. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.10.001 · Cited by 3 · see citing works
Matrix-Bound Nanovesicles: The Extracellular Matrix Vesicle
Leyendecker, P. M., Capella‐Monsonís, H., & Hussey, G. S. (2025) · Biomedical engineering · doi:10.5772/intechopen.1011618 · Cited by 1 · see citing works
Extracellular Vesicles in Regenerative Medicines
Shah, H., Chakraborty, D., Shetty, A., Gopalakrishnan, A. V., Renji, A., Mukherjee, A. G., Wanjari, U. R., Murali, R., & Kannampuzha, S. (2024) · Springer eBooks · doi:10.1007/978-981-97-6270-5_17 · Cited by 1 · see citing works
Dede, E. Ç., Bozbeyoglu, N., Gürsel, İ., Korkusuz, F., Bakan, F., & Korkusuz, P. (2022) · doi:10.22541/au.164873262.20313139/v1
Matrix Bound Nanovesicles Modulatory Effect of Inflammation In Vitro in THP-1 Cells
Giuseppucci, A., Chen, J., Hussey, G. S., & Capella‐Monsonís, H. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18060720
Matrix-bound extracellular vesicles
Celebi, L. E., Hawthorne, L., Higuita‐Castro, N., Gallego‐Perez, D., He, M., Vader, P., Manickam, D. S., Eniola‐Adefeso, L., Cheng, K., & Zorlutuna, P. (2026) · Nature Reviews Bioengineering · doi:10.1038/s44222-026-00477-9
Marques, R. D. R., Baude, J. A., Gathman, G. M., Salami, A. I., Stowers, R. S., & Dewey, M. J. (2026) · Biomaterials Science · doi:10.1039/d6bm00832a
- Authors
- Quijano, L. M., Naranjo, J. D., El-Mossier, S. O., Turner, N. J., Pineda Molina, C., Bartolacci, J., Zhang, L., White, L., Li, H., & Badylak, S. F.
- Affiliations
- University of Pittsburgh (US)
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- University of Nottingham (GB)
- Magee-Womens Research Institute (US)
- Corresponding author
- Badylak, Stephen F.
- ORCID
- Venue
- Tissue Engineering Part C: Methods
- Publisher
- SAGE Publications
- Published
- 2020-10-01
- Volume
- 26
- Issue
- 10
- Pages
- 528-540
- ISSN
- 1937-3384 (ISSN-L)
- 1937-3392
- PMC
- PMC7869881
- OpenAlex
- W3089777907
- Cited by
- 38
- References
- 84
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 8 · 2023: 3 · 2022: 9 · 2021: 2
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Tissue Engineering Part C Methods (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR073527)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- extracellular matrix, collagenase, Liberase, proteinase K, size exclusion chromatography, ultrafiltration, urinary bladder, cellular uptake
- MeSH terms
- Extracellular Vesicles, Endocytosis, Enzymes, Extracellular Matrix, Humans, Particle Size, Peptides, Proteins, Solubility, Stem Cells, MicroRNAs, Cell Proliferation, Nanoparticles
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