Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo
Open accessAbstract
Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs. In this study, we explore the role of bone marrow stromal cell-derived EVs in the regulation of osteoblast activity and bone regeneration. We isolated bone marrow stromal/stem cell (BMSC)-derived EVs through gradient ultracentrifugation and ultrafiltration, and tested the influence of the EVs on osteogenesis both in vivo and in vitro . The results indicated that EVs positively regulated osteogenic genes and osteoblastic differentiation but did not inhibit proliferation in vitro . Furthermore, we constructed an EVs delivery system to stimulate bone formation in Sprague Dawley (SD) rats with calvarial defects. We found that BMSC-derived EVs led to more bone formation in the critical-size calvarial bone defects. Moreover, we found that miR-196a plays an essential role in the regulation of osteoblastic differentiation and the expression of osteogenic genes. We anticipate that our assay using bone marrow stromal cell-derived EVs will become a valuable tool for promoting bone regeneration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pro-osteogenic miRNAs such as miR-196a, miR-27a, and miR-206 are prominent within BM-MSC EVs.
“Additional research emphasizes the prominence of pro-osteogenic miRNAs, such as miR-196a, miR-27a, and miR-206, within BM-MSCs EVs [49,51,52].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [51]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · see citing works
Extracellular vesicles: Exosomes, microvesicles, and friends
Raposo, G., & Stoorvogel, W. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201211138 · Cited by 8,099 · see citing works
Tumour exosome integrins determine organotropic metastasis
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., Di Giannatale, A., Ceder, S., et al. (2015) · Nature · doi:10.1038/nature15756 · Cited by 5,101 · see citing works
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · see citing works
B lymphocytes secrete antigen-presenting vesicles.
Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J. (1996) · The Journal of experimental medicine · doi:10.1084/jem.183.3.1161 · Cited by 3,546 · see citing works
Pan, B., & Johnstone, R. M. (1983) · Cell · doi:10.1016/0092-8674(83)90040-5 · Cited by 2,042 · see citing works
Optimized exosome isolation protocol for cell culture supernatant and human plasma
Lobb, R. J., Becker, M., Wen, S., Wong, C. S. F., Wiegmans, A. P., Leimgruber, A., & Möller, A. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.27031 · Cited by 1,725 · see citing works
Functional delivery of viral miRNAs via exosomes
Pegtel, D. M., Cosmopoulos, K., Thorley‐Lawson, D. A., van Eijndhoven, M. A. J., Hopmans, E. S., Lindenberg, J. L., de Gruijl, T. D., Wurdinger, T. D., & Middeldorp, J. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914843107 · Cited by 1,648 · see citing works
Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells
Morelli, A. E., Larregina, A. T., Shufesky, W. J., Sullivan, M. L. G., Stolz, D. B., Papworth, G. D., Zahorchak, A. F., Logar, A., Wang, Z., Watkins, S. C., et al. (2004) · Blood · doi:10.1182/blood-2004-03-0824 · Cited by 1,075 · see citing works
Molecular Characterization of Dendritic Cell-Derived Exosomes
Théry, C., Régnault, A., Garin, J., Wolfers, J., Zitvogel, L., Ricciardi‐Castagnoli, P., Raposo, G., & Amigorena, S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.3.599 · Cited by 1,065 · see citing works
Lee, C., Mitsialis, S. A., Aslam, M., Vitali, S. H., Vergadi, E., Konstantinou, G., Sdrimas, K., Fernandez‐Gonzalez, A., & Kourembanas, S. (2012) · Circulation · doi:10.1161/circulationaha.112.114173 · Cited by 784 · see citing works
Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission
Alvarez‐Erviti, L., Seow, Y., Schapira, A. H. V., Gardiner, C., Sargent, I. L., Wood, M. J. A., & Cooper, J. A. D. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.029 · Cited by 741 · see citing works
Intestinal epithelial cells secrete exosome–like vesicles
van Niel, G., Raposo, G., Candalh, C., Boussac, M., Hershberg, R. M., Cerf–Bensussan, N., & Heyman, M. (2001) · Gastroenterology · doi:10.1053/gast.2001.26263 · Cited by 698 · see citing works
TCR Activation of Human T Cells Induces the Production of Exosomes Bearing the TCR/CD3/ζ Complex
Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G., & Hivroz, C. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.7.3235 · Cited by 660 · see citing works
Zhou, Y., Xu, H., Xu, W., Wang, B., Wu, H., Tao, Y., Zhang, B., Wang, M., Mao, F., Yan, Y., et al. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt194 · Cited by 647 · see citing works
Plasma Exosomes Protect the Myocardium From Ischemia-Reperfusion Injury
Vicencio, J. M., Yellon, D. M., Sivaraman, V., Das, D. K., Boi-Doku, C., Arjun, S., Zheng, Y. H., Riquelme, J. A., Kearney, J., Sharma, V., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.02.026 · Cited by 541 · see citing works
Follicular Dendritic Cells Carry MHC Class II-Expressing Microvesicles at Their Surface
Denzer, K., van Eijk, M., Kleijmeer, M. J., Jakobson, E., de Groot, C. H., & Geuze, H. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.3.1259 · Cited by 451 · see citing works
Raposo, G., Tenza, D., Mecheri, S., Péronet, R., Bonnerot, C., & Desaymard, C. (1997) · Molecular Biology of the Cell · doi:10.1091/mbc.8.12.2631 · Cited by 406 · see citing works
Osugi, M., Katagiri, W., Yoshimi, R., Inukai, T., Hibi, H., & Ueda, M. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0325 · Cited by 382 · see citing works
Wu, Y., Deng, W., & Klinke, D. J. (2015) · The Analyst · doi:10.1039/c5an00688k · Cited by 368 · see citing works
Adhesion and signaling by B cell‐derived exosomes: the role of integrins
Clayton, A., Turkes, A., Dewitt, S., Steadman, R., Mason, M. D., & Hallett, M. B. (2004) · The FASEB Journal · doi:10.1096/fj.03-1094fje · Cited by 339 · see citing works
Mears, R., Craven, R. A., Hanrahan, S. J., Totty, N., Upton, C., Young, S. L., Patel, P. M., Selby, P. J., & Banks, R. E. (2004) · PROTEOMICS · doi:10.1002/pmic.200400876 · Cited by 335 · see citing works
Chen, L., Charrier, A., Zhou, Y., Chen, R., Yu, B., Agarwal, K., Tsukamoto, H., Lee, J. L., Paulaitis, M. E., & Brigstock, D. R. (2013) · Hepatology · doi:10.1002/hep.26768 · Cited by 264 · see citing works
Li, Y., Fan, L., Liu, S., Liu, W., Zhang, H., Zhou, T., Wu, D., Yang, P., Shen, L., Chen, J., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.052 · Cited by 220 · see citing works
Campanella, C., Bucchieri, F., Merendino, A. M., Fucarino, A., Burgio, G., Corona, D. F. V., Barbieri, G., David, S., Farina, F., Zummo, G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042008 · Cited by 134 · see citing works
Stem cell-derived exosomes: roles in stromal remodeling, tumor progression, and cancer immunotherapy
Fatima, F., & Nawaz, M. (2015) · Chinese journal of cancer · doi:10.1186/s40880-015-0051-5 · Cited by 108 · see citing works
Gene therapy approaches to regenerating bone
Bleich, N. K., Kallai, I., Lieberman, J. R., Schwarz, E. M., Pelled, G., & Gazit, D. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.03.007 · Cited by 86 · see citing works
Emerging Role of Stem Cells - Derived Exosomes as Valuable Tools for Cardiovascular Therapy
Rosca, A., Rayia, D. M. A., & Ţuţuianu, R. (2016) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x10666151026115320 · Cited by 34 · see citing works
Kunkel, N., Wagner, A., Gehwolf, R., Heimel, P., Tempfer, H., Korntner, S. H., Augat, P., Resch, H., Redl, H. R., Betz, O. B., et al. (2015) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2097 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Promoting tissue regeneration by modulating the immune system
Julier, Z., Park, A. J., Briquez, P. S., & Martino, M. M. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.01.056 · Cited by 766 · see citing works
Therapeutically harnessing extracellular vesicles
Cheng, L., & Hill, A. F. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00410-w · Cited by 737 · see citing works
Kou, M., Huang, L., Yang, J., Chiang, Z., Chen, S., Liu, J., Guo, L., Zhang, X., Zhou, X., Xu, X. M., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05034-x · Cited by 655 · see citing works
Toh, W. S., Lai, R. C., Hui, J. H. P., & Lim, S. K. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.11.008 · Cited by 511 · see citing works
Extracellular vesicle-loaded hydrogels for tissue repair and regeneration
Ju, Y., Hu, Y., Pu, Y., Xie, X., & Fang, B. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100522 · Cited by 463 · see citing works
Bone Tissue Engineering in the Treatment of Bone Defects
Xue, N., Ding, X., Huang, R., Jiang, R., Huang, H., Pan, X., Min, W., Chen, J., Duan, J., Liu, P., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15070879 · Cited by 462 · see citing works
Li, W., Liu, Y., Zhang, P., Tang, Y., Zhou, M., Jiang, W., Zhang, X., Wu, G., & Zhou, Y. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b17620 · Cited by 459 · see citing works
Bone physiology as inspiration for tissue regenerative therapies
Lopes, D., Martins‐Cruz, C., Oliveira, M. B., & Mano, J. F. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.09.028 · Cited by 438 · see citing works
Brennan, M. Á., Layrolle, P., & Mooney, D. J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909125 · Cited by 397 · see citing works
Zhang, L., Jiao, G., Ren, S., Zhang, X., Li, C., Wu, W., Wang, H., Liu, H., Zhou, H., & Chen, Y. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-1562-9 · Cited by 360 · see citing works
Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use
Gimona, M., Pachler, K., Laner‐Plamberger, S., Schallmoser, K., & Rohde, E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061190 · Cited by 323 · see citing works
Tsiapalis, D., & O’Driscoll, L. (2020) · Cells · doi:10.3390/cells9040991 · Cited by 312 · see citing works
Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications
Eleuteri, S., & Fierabracci, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184597 · Cited by 302 · see citing works
Dabrowska, S., Andrzejewska, A., Janowski, M., & Łukomska, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.591065 · Cited by 296 · see citing works
Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics
Ponzetti, M., & Rucci, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136651 · Cited by 285 · see citing works
Bjørge, I. M., Kim, S. Y., Mano, J. F., Kalionis, B., & Chrzanowski, W. (2017) · Biomaterials Science · doi:10.1039/c7bm00479f · Cited by 276 · see citing works
Zhang, Y., Hao, Z., Wang, P., Xia, Y. Q., Wu, J., Xia, D., Fang, S., & Xu, S. (2019) · Cell Proliferation · doi:10.1111/cpr.12570 · Cited by 275 · see citing works
Long-term and sequential treatment for osteoporosis
Foessl, I., Dimai, H. P., & Obermayer-Pietsch, B. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00866-9 · Cited by 273 · see citing works
Diomede, F., Gugliandolo, A., Cardelli, P., Merciaro, I., Ettorre, V., Traini, T., Bedini, R., Scionti, D., Bramanti, A., Nanci, A., et al. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0850-0 · Cited by 269 · see citing works
Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies
Chang, C. K. W., Yan, J., Yao, Z., Zhang, C., Li, X., & Mao, H. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202001689 · Cited by 253 · see citing works
Self-citationSustained Delivery System for Stem Cell-Derived Exosomes
Riau, A. K., Ong, H. S., Yam, G. H., & Mehta, J. S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01368 · Cited by 238 · see citing works
Hydrogel Encapsulation of Mesenchymal Stem Cells and Their Derived Exosomes for Tissue Engineering
Khayambashi, P., Iyer, J. S., Pillai, S., Upadhyay, A., Zhang, Y., & Tran, S. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020684 · Cited by 235 · see citing works
Ciferri, M. C., Quarto, R., & Tasso, R. (2021) · Biology · doi:10.3390/biology10050359 · Cited by 231 · see citing works
To Protect and to Preserve: Novel Preservation Strategies for Extracellular Vesicles
Kusuma, G. D., Barabadi, M., Tan, J. L., Morton, D. A. V., Frith, J. E., & Lim, R. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01199 · Cited by 222 · see citing works
Takeuchi, R., Katagiri, W., Endo, S., & Kobayashi, T. (2019) · PLOS ONE · doi:10.1371/journal.pone.0225472 · Cited by 210 · see citing works
Extracellular vesicles for tissue repair and regeneration: Evidence, challenges and opportunities
Nagelkerke, A., Ojansivu, M., van der Koog, L., Whittaker, T. E., Cunnane, E. M., da Silva, A. M., Dekker, N., & Stevens, M. M. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.04.013 · Cited by 208 · see citing works
Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine
González-González, A., García‐Sánchez, D., Dotta, M., Rodríguez-Rey, J. C., & Pérez-Campo, F. M. (2020) · World Journal of Stem Cells · doi:10.4252/wjsc.v12.i12.1529 · Cited by 206 · see citing works
Liu, A., Lin, D., Zhao, H., Chen, L., Cai, B., Lin, K., & Shen, S. G. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120718 · Cited by 201 · see citing works
Lee, K. S., Lee, J., Kim, H. K., Yeom, S. H., Woo, C. H., Jung, Y. J., Yun, Y. E., Park, S. Y., Han, J., Kim, E., et al. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12152 · Cited by 200 · see citing works
Functionally engineered extracellular vesicles improve bone regeneration
Huang, C.-C., Kang, M., Lu, Y., Shirazi, S., Iriarte-Díaz, J., Cooper, L. F., Gajendrareddy, P. K., & Ravindran, S. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.04.017 · Cited by 191 · see citing works
Qin, Y., Sun, R., Wu, C., Wang, L. Y., & Zhang, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050712 · Cited by 185 · see citing works
Self-citationThe roles of bone‐derived exosomes and exosomal micro RNA s in regulating bone remodelling
Xie, Y., Chen, Y., Zhang, L., Ge, W., & Tang, P. (2016) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13039 · Cited by 179 · see citing works
Liu, L., Guo, S., Shi, W., Liu, Q., Huo, F., Wu, Y., & Tian, W. (2020) · Tissue Engineering Part A · doi:10.1089/ten.tea.2020.0141 · Cited by 176 · see citing works
Technological advances towards extracellular vesicles mass production
Grangier, A., Branchu, J., Volatron, J., Piffoux, M., Gazeau, F., Wilhelm, C., & Silva, A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113843 · Cited by 176 · see citing works
Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration
Levingstone, T. J., Herbaj, S., & Dunne, N. (2019) · Nanomaterials · doi:10.3390/nano9111570 · Cited by 175 · see citing works
Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy
Kushioka, J., Chow, S. K., Toya, M., Tsubosaka, M., Shen, H., Gao, Q., Li, X., Zhang, N., & Goodman, S. B. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00279-1 · Cited by 174 · see citing works
Hu, Y., Zhang, Y., Ni, C.-Y., Chen, C., Rao, S., Yin, H., Huang, J., Tan, Y., Wang, Z., Cao, J., et al. (2020) · Theranostics · doi:10.7150/thno.39238 · Cited by 170 · see citing works
Lipid, Protein, and MicroRNA Composition Within Mesenchymal Stem Cell-Derived Exosomes
Deng, H., Sun, C., Sun, Y., Li, H., Yang, L., Wu, D., Gao, Q., & Jiang, X. (2018) · Cellular Reprogramming · doi:10.1089/cell.2017.0047 · Cited by 155 · see citing works
Marolt, D., Traweger, A., Gimona, M., & Redl, H. R. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00352 · Cited by 153 · see citing works
A New Self-Healing Hydrogel Containing hucMSC-Derived Exosomes Promotes Bone Regeneration
Wang, L., Wang, J., Zhou, X., Sun, J., Zhu, B., Duan, C., Chen, P., Guo, X., Zhang, T., & Guo, H. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.564731 · Cited by 153 · see citing works
Self-citationEmerging Role of Extracellular Vesicles in Bone Remodeling
Liu, M., Sun, Y., & Zhang, Q. (2018) · Journal of Dental Research · doi:10.1177/0022034518764411 · Cited by 142 · see citing works
Wu, J., Chen, L., Wang, R., Song, Z., Shen, Z., Zhao, Y., Huang, S., & Lin, Z. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b00607 · Cited by 140 · see citing works
New therapeutic approaches of mesenchymal stem cells-derived exosomes
Janočková, J., Slovinská, L., Harvanová, D., Špaková, T., & Rosocha, J. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00736-4 · Cited by 140 · see citing works
Cai, J., Wu, J., Wang, J., Li, Y., Hu, X.-B., Luo, S., & Xiang, D. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00427-x · Cited by 137 · see citing works
Biomass Microcapsules with Stem Cell Encapsulation for Bone Repair
Yang, L., Liu, Y., Sun, L., Zhao, C., Chen, G., & Zhao, Y. (2021) · Nano-Micro Letters · doi:10.1007/s40820-021-00747-8 · Cited by 135 · see citing works
Self-citationFoo, J. B., Looi, Q. H., Chong, P. P., Hassan, N. H., Yeo, G. E. C., Ng, C. Y., Koh, B., How, C. W., Lee, S. H., & Law, J. X. (2021) · Stem Cells International · doi:10.1155/2021/2616807 · Cited by 131 · see citing works
The advances in nanomedicine for bone and cartilage repair
Qiao, K., Xu, L., Tang, J., Wang, Q., Lim, K. S., Hooper, G. J., Woodfield, T. B. F., Liu, G., Tian, K., Zhang, W., et al. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01342-8 · Cited by 131 · see citing works
Stem Cell-Derived Extracellular Vesicles as a Novel Potential Therapeutic Tool for Tissue Repair
Chen, B., Li, Q., Zhao, B., & Wang, Y. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.16-0477 · Cited by 129 · see citing works
3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels
Huang, C.-C., Kang, M., Shirazi, S., Lu, Y., Cooper, L. F., Gajendrareddy, P. K., & Ravindran, S. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.030 · Cited by 129 · see citing works
Roszkowski, S. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01282-z · Cited by 129 · see citing works
Exosomes—the enigmatic regulators of bone homeostasis
Gao, M., Gao, W., Papadimitriou, J. M., Zhang, C., Gao, J., & Zheng, M. (2018) · Bone Research · doi:10.1038/s41413-018-0039-2 · Cited by 128 · see citing works
Self-citationXu, T., Luo, Y., Wang, J., Zhang, N., Gu, C., Li, L., Qian, D., Cai, W., Fan, J., & Yin, G. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00601-w · Cited by 128 · see citing works
Nizamudeen, Z. A., Márkus, R., Lodge, R. W., Parmenter, C. D. J., Platt, M., Chakrabarti, L., & Sottile, V. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.09.008 · Cited by 125 · see citing works
Malekpour, K., Hazrati, A., Zahar, M., Markov, A. A., Zekiy, A. O., Navashenaq, J. G., Roshangar, L., & Ahmadi, M. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10185-z · Cited by 119 · see citing works
Extracellular Vesicles: Immunomodulatory messengers in the context of tissue repair/regeneration
da Silva, A. M., Teixeira, J. H., Almeida, M. I., Gonçalves, R. M., Barbosa, M. A., & Santos, S. G. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.09.017 · Cited by 118 · see citing works
Current Trends and Future Perspective of Mesenchymal Stem Cells and Exosomes in Corneal Diseases
Mansoor, H., Ong, H. S., Riau, A. K., Stanzel, T. P., Mehta, J. S., & Yam, G. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122853 · Cited by 115 · see citing works
Fatima, F., Ekström, K. M., Nazarenko, I. A., Maugeri, M., Valadi, H., Hill, A. F., Camussi, G., & Nawaz, M. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00161 · Cited by 114 · see citing works
Zhang, X., Wang, Y., Zhao, H., Han, X., Zhao, T., Qu, P., Li, G., & Wang, W. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01707-6 · Cited by 114 · see citing works
Zhang, Y., Yu, M., Dai, M., Chen, C., Tang, Q., Jing, W., Wang, H., & Tian, W. (2017) · Journal of Cell Science · doi:10.1242/jcs.197764 · Cited by 113 · see citing works
Adipose-Derived Stem Cells in Bone Tissue Engineering: Useful Tools with New Applications
Storti, G., Scioli, M. G., Kim, B., Orlandi, A., & Cervelli, V. (2019) · Stem Cells International · doi:10.1155/2019/3673857 · Cited by 109 · see citing works
Tissue Engineering for the Temporomandibular Joint
Acri, T. M., Shin, K., Seol, D., Laird, N. Z., Song, I., Geary, S. M., Chakka, L. R. J., Martin, J. A., & Salem, A. K. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801236 · Cited by 108 · see citing works
Hydrogels for Exosome Delivery in Biomedical Applications
Xie, Y., Guan, Q., Guo, J., Chen, Y., Yin, Y., & Han, X. (2022) · Gels · doi:10.3390/gels8060328 · Cited by 108 · see citing works
Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration
Wang, X., Zeng, J., Gan, D., Ling, K., He, M., Li, J., & Lu, Y. (2024) · Nano-Micro Letters · doi:10.1007/s40820-024-01557-4 · Cited by 108 · see citing works
Targeted delivery of extracellular vesicles in heart injury
Chen, P., Wang, L., Fan, X., Ning, X., Yu, B., Ou, C., & Chen, M. (2020) · Theranostics · doi:10.7150/thno.51571 · Cited by 107 · see citing works
Self-citationStem cell‐derived exosomes: A promising strategy for fracture healing
Hao, Z., Lu, J., Wang, S., Wu, H., Zhang, Y., & Xu, S. (2017) · Cell Proliferation · doi:10.1111/cpr.12359 · Cited by 106 · see citing works
Bone tissue engineering strategy based on the synergistic effects of silicon and strontium ions
Xing, M., Wang, X., Wang, E., Gao, L., & Chang, J. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.03.051 · Cited by 106 · see citing works
Zhang, D., Wu, Y., Li, Z., Chen, H., Huang, S., Jian, C., & Yu, A. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00964-8 · Cited by 106 · see citing works
Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications
Man, K., Brunet, M. Y., Jones, M., & Cox, S. C. (2020) · Nanomaterials · doi:10.3390/nano10091838 · Cited by 105 · see citing works
Pizzicannella, J., Diomede, F., Gugliandolo, A., Chiricosta, L., Bramanti, P., Merciaro, I., Orsini, T., Mazzon, E., & Trubiani, O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133256 · Cited by 104 · see citing works
Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair
Nargesi, A. A., Lerman, L. O., & Eirin, A. (2017) · Current Gene Therapy · doi:10.2174/1566523217666170412110724 · Cited by 103 · see citing works
Exosomes: Mediators of bone diseases, protection, and therapeutics potential
Behera, J., & Tyagi, N. (2018) · Oncoscience · doi:10.18632/oncoscience.421 · Cited by 101 · see citing works
Roles and Regulation of Extracellular Vesicles in Cardiovascular Mineral Metabolism
Blaser, M. C., & Aïkawa, E. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00187 · Cited by 101 · see citing works
Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases
Alcaraz, M. J., Álvaro Compan, J., & Guillén, M. I. (2019) · Cells · doi:10.3390/cells9010098 · Cited by 101 · see citing works
Gualerzi, A., Kooijmans, S. A. A., Niada, S., Picciolini, S., Brini, A. T., Camussi, G., & Bedoni, M. (2019) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2019.1568780 · Cited by 99 · see citing works
Diomede, F., D’Aurora, M., Gugliandolo, A., Merciaro, I., Ettorre, V., Bramanti, A., Piattelli, A., Gatta, V., Mazzon, E., Fontana, A., et al. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s162836 · Cited by 98 · see citing works
Exosomes and Extracellular RNA in Muscle and Bone Aging and Crosstalk
Qin, W., & Dallas, S. L. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00537-7 · Cited by 93 · see citing works
Chen, L., Qu, J., Mei, Q., Chen, X., Fang, Y., Chen, L., Li, Y., & Xiang, C. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02511-6 · Cited by 91 · see citing works
Bone Scaffolds: An Incorporation of Biomaterials, Cells, and Biofactors
Bahraminasab, M., Janmohammadi, M., Arab, S., Talebi, A., Nooshabadi, V. T., Koohsarian, P., & Nourbakhsh, M. S. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00920 · Cited by 90 · see citing works
The role of microRNAs in bone development
Bell‐Hensley, A., & McAlinden, A. (2020) · Bone · doi:10.1016/j.bone.2020.115760 · Cited by 89 · see citing works
Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal Cell recruitment
da Silva, A. M., Almeida, M. I., Teixeira, J. H., Maia, A. F., Călin, G. A., Barbosa, M. A., & Santos, S. G. (2017) · Scientific Reports · doi:10.1038/s41598-017-01809-x · Cited by 88 · see citing works
Application of engineered extracellular vesicles for targeted tumor therapy
Zhang, F., Guo, J. J., Zhang, Z., Duan, M., Wang, G., Qian, Y., Zhao, H., Yang, Z., & Jiang, X. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00798-y · Cited by 85 · see citing works
Human perivascular stem cell-derived extracellular vesicles mediate bone repair
Xu, J., Wang, Y., Hsu, C.-Y., Gao, Y., Meyers, C. A., Chang, L., Zhang, L., Broderick, K. P., Ding, C., Péault, B., et al. (2019) · eLife · doi:10.7554/elife.48191 · Cited by 84 · see citing works
Advances in extracellular vesicle functionalization strategies for tissue regeneration
Zheng, D., Ruan, H., Chen, W., Zhang, Y., Cui, W., Chen, H., & Shen, H. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.07.022 · Cited by 81 · see citing works
Biomaterial-based extracellular vesicle delivery for therapeutic applications
Priya, M. V., & Holmes, C. A. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.010 · Cited by 79 · see citing works
Munoz-Perez, E., Gonzalez‐Pujana, A., Igartúa, M., Santos‐Vizcaíno, E., & Hernández, R. M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111802 · Cited by 78 · see citing works
Effects of BMSC-Derived EVs on Bone Metabolism
Zhou, X., Cao, H., Guo, J., Yuan, Y. J., & Ni, G. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14051012 · Cited by 78 · see citing works
Zhu, Z., Zhang, Y., Zhang, Y., Zhang, H., Liu, W., Zhang, N., Zhang, X., Zhou, G., Wu, L., Hua, K., et al. (2018) · Human Reproduction · doi:10.1093/humrep/dey344 · Cited by 78 · see citing works
Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges
Fuloria, S., Subramaniyan, V., Dahiya, R., Dahiya, S., Sudhakar, K., Kumari, U., Sathasivam, K. V., Meenakshi, D. U., Wu, Y. S., Sekar, M., et al. (2021) · Biology · doi:10.3390/biology10030172 · Cited by 76 · see citing works
Liu, T., Hu, W., Zou, X., Xu, J., He, S., Chang, L., Li, X., Yin, Y., Tian, M., Li, Z., et al. (2020) · Stem Cells International · doi:10.1155/2020/8852307 · Cited by 75 · see citing works
Wang, L. Y., Shang, Z., Zhou, Y., Hu, X., Chen, Y., Fan, Y., Wei, X., Wu, L. L., Liang, Q., Zhang, J., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0242-x · Cited by 75 · see citing works
Self-citationHu, Y., Xu, R., Chen, C., Rao, S., Xia, K., Huang, J., Yin, H., Wang, Z., Cao, J., Liu, Z., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.01.009 · Cited by 75 · see citing works
Wang, N., Liu, X., Tang, Z., Wei, X., Dong, H., Liu, Y., Wu, H., Wu, Z., Li, X., Ma, X., et al. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01267-2 · Cited by 74 · see citing works
Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration
Torrecillas-Baena, B., Pulido-Escribano, V., Dorado, G., Gálvez-Moreno, M. Á., Camacho-Cardeñosa, M., & Casado‐Díaz, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12134385 · Cited by 74 · see citing works
Man, K., Brunet, M. Y., Fernández‐Rhodes, M., Williams, S., Heaney, L. M., Gethings, L. A., Federici, A., Davies, O. G., Hoey, D. A., & Cox, S. C. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12118 · Cited by 73 · see citing works
Mesenchymal Stem Cell-Derived Extracellular Vesicles for Bone Defect Repair
Wang, D., Cao, H., Hua, W., Gao, L., Yuan, Y. J., Zhou, X., & Zeng, Z. (2022) · Membranes · doi:10.3390/membranes12070716 · Cited by 73 · see citing works
Li, X., Si, Y., Liang, J., Li, M., Wang, Z., Qin, Y., & Sun, L. (2024) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2024.05.209 · Cited by 72 · see citing works
Self-citationStem cell secretome, regeneration, and clinical translation: a narrative review
Gwam, C., Mohammed, N., & Ma, X. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-5030 · Cited by 72 · see citing works
The role and therapeutic potential of MSC-derived exosomes in osteoarthritis
Bao, C., & He, C. (2021) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2021.109002 · Cited by 72 · see citing works
Exosomes: A Novel Therapeutic Agent for Cartilage and Bone Tissue Regeneration
Liu, Y., Ma, Y., Zhang, J., Yuan, Y., & Wang, J. (2019) · Dose-Response · doi:10.1177/1559325819892702 · Cited by 69 · see citing works
Zhang, H., Li, X., Li, J., Zhong, L., Chen, X., & Chen, S. (2020) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-020-01122-0 · Cited by 69 · see citing works
- Authors
- Qin, Y., Wang, L., Gao, Z., Chen, G., & Zhang, C.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Tongji University (CN)
- Guangdong Medical College (CN)
- Corresponding author
- Chen, Genyin
- Zhang, Changqing
- Venue
- Scientific Reports
- Published
- 2016-02-25
- Volume
- 6
- Issue
- 1
- Pages
- 21961-21961
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4766421
- OpenAlex
- W2417871706
- Cited by
- 458
- References
- 29
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 45 · 2023: 53 · 2022: 61 · 2021: 84 · 2020: 59 · 2019: 41 · 2018: 28 · 2017: 23 · 2016: 5
- FWCI
- 16.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- extracellular vesicles, mesenchymal stem cells, osteogenic differentiation, bone formation, bone regeneration, miR-196a, calvarial defect, critical-size bone defect, osteogenic gene expression
- MeSH terms
- Extracellular Vesicles, Animals, Bone and Bones, Bone Marrow Cells, Bone Regeneration, Cell Differentiation, Cells, Cultured, Endoplasmic Reticulum, Flow Cytometry, Golgi Apparatus, Humans, Male, Microscopy, Electron, Osteoblasts, Osteogenesis, Osteocalcin, Rats, Sprague-Dawley, Microscopy, Confocal, MicroRNAs, Rats, Osteopontin, X-Ray Microtomography, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
