Exosomes from conditioned media of bone marrow-derived mesenchymal stem cells promote bone regeneration by enhancing angiogenesis
Open accessAbstract
Growth factors in serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (MSC-CM) are known to be effective in bone regeneration. However, the secretomes in MSC-CM that act as active ingredients for bone regeneration, as well as their mechanisms, remains unclear. Exosomes, components of MSC-CM, provide the recipient cells with genetic information and enhance the recipient cellular paracrine stimulation, which contributes to tissue regeneration. We hypothesized that MSC-CM-derived exosomes (MSC-Exo) promoted bone regeneration, and that angiogenesis was a key step. Here, we prepared an MSC-Exo group, MSC-CM group, and Exo-antiVEGF group (MSC-Exo with angiogenesis inhibitor), and examined the osteogenic and angiogenic potential in MSCs. Furthermore, we used a rat model of calvaria bone defect and implanted each sample to evaluate bone formation weekly, until week 4 after treatment. Results showed that MSC-Exo enhanced cellular migration and osteogenic and angiogenic gene expression in MSCs compared to that in other groups. In vivo, early bone formation by MSC-Exo was also confirmed. Two weeks after implantation, the newly formed bone area was 31.5 ± 6.5% in the MSC-Exo group while those in the control and Exo-antiVEGF groups were 15.4 ± 4.4% and 8.7 ± 1.1%, respectively. Four weeks after implantation, differences in the area between the MSC-Exo group and the Exo-antiVEGF or control groups were further broadened. Histologically, notable accumulation of osteoblast-like cells and vascular endothelial cells was observed in the MSC-Exo group; however, fewer cells were found in the Exo-antiVEGF and control groups. In conclusion, MSC-Exo promoted bone regeneration during early stages, as well as enhanced angiogenesis. Considering the tissue regeneration with transplanted cells and their secretomes, this study suggests that exosomes might play an important role, especially in angiogenesis.
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Osteogenesis is closely related with vascularization due to cell-to-cell communication between vascular endothelial cells and osteoblasts.
“osteogenesis is closely related with vascularization due to cell-to-cell communication between vascular endothelial cells and osteoblasts [99].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [99]
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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
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
Vascular endothelial growth factor (VEGF) and its receptors
Neufeld, G., Cohen, T., Gengrinovitch, S., & Gluzman‐Poltorak, Z. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.1.9 · Cited by 3,488 · see citing works
Basic and Therapeutic Aspects of Angiogenesis
Potente, M., Gerhardt, H., & Carmeliet, P. (2011) · Cell · doi:10.1016/j.cell.2011.08.039 · Cited by 2,771 · see citing works
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2009.12.003 · Cited by 2,215 · see citing works
Vascularization in tissue engineering
Rouwkema, J., Rivron, N. C., & van Blitterswijk, C. (2008) · Trends in biotechnology · doi:10.1016/j.tibtech.2008.04.009 · Cited by 1,218 · see citing works
Mesenchymal stem cells: a new trend for cell therapy
Wei, X., Yang, X. F., Han, Z., Qu, F.-F., Shao, L., & Shi, Y. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.50 · Cited by 945 · see citing works
Exosomes Derived from Mesenchymal Stem Cells
Yu, B., Zhang, X., & Li, X. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15034142 · Cited by 788 · see citing works
Zhang, Y., Chopp, M., Meng, Y., Katakowski, M., Xin, H., Mahmood, A., & Xiong, Y. (2015) · Journal of neurosurgery · doi:10.3171/2014.11.jns14770 · Cited by 737 · see citing works
Samsonraj, R. M., Raghunath, M., Nurcombe, V., Hui, J. H. P., van Wijnen, A. J., & Cool, S. M. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0129 · Cited by 732 · see citing works
Regenerative Effects of Transplanted Mesenchymal Stem Cells in Fracture Healing
Granero‐Moltó, F., Weis, J. A., Miga, M. I., Landis, B. J., Myers, T. J., O’Rear, L., Longobardi, L., Jansen, D., Mortlock, D. P., & Spagnoli, A. (2009) · Stem Cells · doi:10.1002/stem.103 · Cited by 530 · see citing works
Exosomes: From Garbage Bins to Promising Therapeutic Targets
Rashed, M. H., Bayraktar, E., Helal, G. K., Abd‐Ellah, M. F., Amero, P., Chávez‐Reyes, A., & Rodriguez‐Aguayo, C. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030538 · Cited by 525 · see citing works
Qin, Y., Wang, L., Gao, Z., Chen, G., & Zhang, C. (2016) · Scientific Reports · doi:10.1038/srep21961 · Cited by 458 · see citing works
Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model
Furuta, T., Miyaki, S., Ishitobi, H., Ogura, T., Kato, Y., Kamei, N., Miyado, K., Higashi, Y., & Ochi, M. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0285 · Cited by 444 · 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
Self-citationRole of angiogenesis in bone repair
Saran, U., Piperni, S. G., & Chatterjee, S. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.07.006 · Cited by 362 · see citing works
Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Izadpanah, R., Kaushal, D., Kriedt, C. L., Tsien, F., Patel, B. G., Dufour, J., & Bunnell, B. A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5272 · Cited by 352 · see citing works
Chen, S., Tang, Y., Liu, Y., Zhang, P., Lv, L., Zhang, X., Jia, L., & Zhou, Y. (2019) · Cell Proliferation · doi:10.1111/cpr.12669 · Cited by 344 · see citing works
Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration
Linero, I., & Chaparro, O. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107001 · Cited by 323 · see citing works
Sun, G., Li, G., Li, D., Huang, W., Zhang, R., Zhang, H., Duan, Y., & Wang, B. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.04.006 · Cited by 314 · see citing works
Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation
Nishida, S., Endo, N., Yamagiwa, H., Tanizawa, T., & Takahashi, H. E. (1999) · Journal of Bone and Mineral Metabolism · doi:10.1007/s007740050081 · Cited by 303 · see citing works
Dalirfardouei, R., Jamialahmadi, K., Jafarian, A. H., & Mahdipour, E. (2019) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2799 · Cited by 220 · see citing works
Mendes, S. C., Tibbe, J. M., Veenhof, M., Bakker, K., Both, S. K., Platenburg, P. P., Öner, F. C., de Bruijn, J. D., & van Blitterswijk, C. (2002) · Tissue Engineering · doi:10.1089/107632702320934010 · Cited by 215 · see citing works
Gangadaran, P., Rajendran, R. L., Lee, H., Kalimuthu, S., Hong, C. M., Jeong, S. Y., Lee, S., Lee, J., & Ahn, B. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.08.022 · Cited by 212 · see citing works
Stem Cell Therapy for Craniofacial Bone Regeneration: A Randomized, Controlled Feasibility Trial
Kaigler, D., Pagni, G., Park, C. H., Braun, T., Holman, L. A., Yi, E., Tarlé, S. A., Bartel, R. L., & Giannobile, W. V. (2013) · Cell Transplantation · doi:10.3727/096368912x652968 · Cited by 196 · see citing works
Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration
Liu, S., Zhou, J., Zhang, X., Liu, Y., Chen, J., Hu, B., Song, J., & Zhang, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060982 · Cited by 177 · see citing works
Wang, X., Omar, O., Vazirisani, F., Thomsen, P., & Ekström, K. (2018) · PLoS ONE · doi:10.1371/journal.pone.0193059 · Cited by 176 · see citing works
Pacelli, S., Basu, S., Whitlow, J., Chakravarti, A. R., Acosta, F. M., Varshney, A., Modaresi, S., Berkland, C. J., & Paul, A. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.07.011 · Cited by 166 · see citing works
Kumar, S., Wan, C., Ramaswamy, G., Clemens, T. L., & Ponnazhagan, S. (2010) · Molecular Therapy · doi:10.1038/mt.2009.315 · Cited by 161 · see citing works
Rickert, D., Sauerbier, S., Nagursky, H., Menne, D., Vissink, A., & Raghoebar, G. M. (2010) · Clinical Oral Implants Research · doi:10.1111/j.1600-0501.2010.01981.x · Cited by 144 · see citing works
Kawai, T., Katagiri, W., Osugi, M., Sugimura, Y., Hibi, H., & Ueda, M. (2015) · Cytotherapy · doi:10.1016/j.jcyt.2014.11.009 · Cited by 141 · see citing works
Self-citationJafarian, M., Eslaminejad, M. B., Khojasteh, A., Abbas, F. M., Dehghan, M. M., Hassanizadeh, R., & Houshmand, B. (2008) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/j.tripleo.2008.01.010 · Cited by 134 · see citing works
Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases
Fleury, A., Martínez, M. C., & Lay, S. L. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00370 · Cited by 125 · see citing works
Katagiri, W., Osugi, M., Kawai, T., & Hibi, H. (2016) · Head & Face Medicine · doi:10.1186/s13005-016-0101-5 · Cited by 122 · see citing works
Self-citationPelegrine, A. A., da Costa, C. E. S., Corrêa, M. E. P., & Marques, J. F. C. (2010) · Clinical Oral Implants Research · doi:10.1111/j.1600-0501.2009.01891.x · Cited by 120 · see citing works
Cell Sources for Bone Regeneration: The Good, the Bad, and the Ugly (But Promising)
Robey, P. G. (2011) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2011.0199 · Cited by 114 · see citing works
Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells
Katagiri, W., Kawai, T., Osugi, M., Sugimura, Y., Sakaguchi, K., Kojima, T., & Kobayashi, T. (2017) · Maxillofacial Plastic and Reconstructive Surgery · doi:10.1186/s40902-017-0106-4 · Cited by 91 · see citing works
Self-citationKatagiri, W., Watanabe, J., Toyama, N., Osugi, M., Sakaguchi, K., & Hibi, H. (2017) · Implant Dentistry · doi:10.1097/id.0000000000000618 · Cited by 91 · see citing works
Self-citationGranero‐Moltó, F., Myers, T. J., Weis, J. A., Longobardi, L., Li, T., Yan, Y., Case, N. D., Rubin, J. E., & Spagnoli, A. (2011) · Stem Cells · doi:10.1002/stem.697 · Cited by 89 · see citing works
Watson, L., Elliman, S. J., & Coleman, C. M. (2014) · Stem Cell Research & Therapy · doi:10.1186/scrt439 · Cited by 86 · see citing works
Guiducci, S., Manetti, M., Romano, E., Mazzanti, B., Ceccarelli, C., Pozzo, S. D., Milia, A. F., Bellando-Randone, S., FIORI, G., Conforti, M. L., et al. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2011.150607 · Cited by 84 · see citing works
Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering
Paino, F., Noce, M. L., Giuliani, A., ROSA, A. D., Mazzoni, S., Laino, L., Amler, E., Papaccio, G., Desiderio, V., & Tirino, V. (2017) · Clinical Science · doi:10.1042/cs20170047 · Cited by 84 · see citing works
Fennema, E. M., Tchang, L., Yuan, H., van Blitterswijk, C., Martín, I., Scherberich, A., & de Boer, J. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2453 · Cited by 82 · see citing works
VEGF stimulates intramembranous bone formation during craniofacial skeletal development
Duan, X., Bradbury, S. R., Olsen, B. R., & Berendsen, A. D. (2016) · Matrix Biology · doi:10.1016/j.matbio.2016.02.005 · Cited by 78 · see citing works
Novel Cell-Free Regeneration of Bone Using Stem Cell–Derived Growth Factors
Katagiri, W., Osugi, M., Kawai, T., & Ueda, M. (2013) · The International Journal of Oral & Maxillofacial Implants · doi:10.11607/jomi.3036 · Cited by 70 · see citing works
Self-citationCell‐to‐cell communication in guided bone regeneration: molecular and cellular mechanisms
Gruber, R., Stadlinger, B., & Terheyden, H. (2016) · Clinical Oral Implants Research · doi:10.1111/clr.12929 · Cited by 67 · see citing works
Vertical bone regeneration using rhBMP-2 and VEGF
Schorn, L., Sproll, C. K., Ommerborn, M. A., Naujoks, C. D., Kübler, N. R., & Depprich, R. A. (2017) · Head & Face Medicine · doi:10.1186/s13005-017-0146-0 · Cited by 67 · see citing works
Targeting stem cell niches and trafficking for cardiovascular therapy
Kränkel, N., Spinetti, G., Amadesi, S., & Madeddu, P. R. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.10.002 · Cited by 42 · see citing works
Katagiri, W., Sakaguchi, K., Kawai, T., Wakayama, Y., Osugi, M., & Hibi, H. (2017) · Cell Proliferation · doi:10.1111/cpr.12333 · Cited by 40 · see citing works
Self-citationKodama, A., Kamei, N., Kamei, G., Kongcharoensombat, W., Ohkawa, S., Nakabayashi, A., & Ochi, M. (2012) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.94b7.28521 · Cited by 37 · see citing works
Ogata, K., Osugi, M., Kawai, T., Wakayama, Y., Sakaguchi, K., Nakamura, S., & Katagiri, W. (2018) · Journal of Oral and Maxillofacial Surgery Medicine and Pathology · doi:10.1016/j.ajoms.2018.04.002 · Cited by 26 · see citing works
Self-citationMicroRNA-378 Promotes Osteogenesis-Angiogenesis Coupling in BMMSCs for Potential Bone Regeneration
Zhang, B., Li, Y., Yu, Y., Zhao, J., Ou, Y., Chao, Y., Yang, B.-H., & Yu, X. (2018) · Analytical Cellular Pathology · doi:10.1155/2018/8402390 · Cited by 24 · see citing works
Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment
Dicarlo, M., Bianchi, N., Ferretti, C., Orciani, M., Primio, R. D., & Mattioli‐Belmonte, M. (2016) · Cells Tissues Organs · doi:10.1159/000445346 · Cited by 21 · see citing works
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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
Mesenchymal stem cells: Amazing remedies for bone and cartilage defects
Kangari, P., Talaei-Khozani, T., Razeghian-Jahromi, I., & Razmkhah, M. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02001-1 · Cited by 286 · 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
Wu, D., Chang, X., Tian, J., Kang, L., Wu, Y., Liu, J., Wu, X., Huang, Y., Gao, B., Wang, H., et al. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00958-6 · Cited by 263 · see citing works
Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?
Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.004 · Cited by 205 · see citing works
“In fact, osteogenesis is closely related with vascularization due to cell-to-cell communication between vascular endothelial cells and osteoblasts [99].”
Maqsood, M., Kang, M., Wu, X., Chen, J., Teng, L., & Qiu, L. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118002 · Cited by 205 · 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
Hoang, D. H., Nguyen, T. D., Nguyen, H.-P., Nguyen, X., Do, P. T. X., Dang, V. D., Dam, P. T. M., Bui, H. T. H., Trinh, M. Q., Vu, D. M., et al. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00119 · Cited by 169 · see citing works
Tan, S. H. S., Wong, J. R. Y., Sim, S. J. Y., Tjio, C. K. E., Wong, K. L., Chew, J. R. J., Hui, J. H. P., & Toh, W. S. (2020) · Materials Today Bio · doi:10.1016/j.mtbio.2020.100067 · Cited by 152 · see citing works
Application of stem cells in regeneration medicine
Jin, Y. H., Li, S., Yu, Q., Chen, T., & Liu, D. (2023) · MedComm · doi:10.1002/mco2.291 · Cited by 141 · 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
Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials
Gugliandolo, A., Fonticoli, L., Trubiani, O., Rajan, T. S., Marconi, G. D., Bramanti, P., Mazzon, E., Pizzicannella, J., & Diomede, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105236 · Cited by 110 · see citing works
Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics
Ansari, S., de Wildt, B. W. M., Vis, M. A. M., de Korte, C. E., Ito, K., Hofmann, S., & Yuana, Y. (2021) · Pharmaceuticals · doi:10.3390/ph14040289 · Cited by 101 · see citing works
Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade
Moghassemi, S., Dadashzadeh, A., Sousa, M. J., Vlieghe, H., Yang, J., León-Félix, C. M., & Amorim, C. A. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.02.021 · Cited by 107 · see citing works
MSCs vs. iPSCs: Potential in therapeutic applications
Thanaskody, K., Jusop, A. S., Tye, G. J., Zaman, W. S. W. K., Dass, S. A., & Nordin, F. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1005926 · Cited by 102 · see citing works
Understanding exosomes: Part 1—Characterization, quantification and isolation techniques
Miron, R. J., & Zhang, Y. (2023) · Periodontology 2000 · doi:10.1111/prd.12520 · Cited by 96 · see citing works
Understanding exosomes: Part 2—Emerging leaders in regenerative medicine
Miron, R. J., Estrin, N. E., Sculean, A., & Zhang, Y. (2024) · Periodontology 2000 · doi:10.1111/prd.12561 · Cited by 83 · 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
Sun, J., Sun, X., Chen, J., Liao, X., He, Y., Wang, J., Chen, R., Hu, S., & Qiu, C. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02068-w · Cited by 78 · see citing works
Ying, C., Wang, R., Wang, Z., Tao, J., Yin, W., Zhang, J., Yi, C., Qi, X., & Han, D. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.565561 · Cited by 75 · 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
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
Engineered extracellular vesicles for bone therapy
Jiang, Y., Li, J., Xu, X. J., Yin, Z., Xu, K., & Su, J. (2022) · Nano Today · doi:10.1016/j.nantod.2022.101487 · Cited by 68 · see citing works
Williams, T., Salmanian, G., Burns, M., Maldonado, V. V., Smith, E., Porter, R. M., Song, Y. H., & Samsonraj, R. M. (2022) · Biochimie · doi:10.1016/j.biochi.2022.11.011 · Cited by 69 · see citing works
Exosomes and Their Role in Cancer Progression
Liu, Y., Shi, K., Chen, Y., Wu, X.-R., Chen, Z., Cao, K., Tao, Y.-G., Chen, X., Liao, J., & Zhou, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.639159 · Cited by 37 · see citing works
Gao, W., He, R., Ren, J., Zhang, W., Wang, K., Zhu, L., & Liang, T. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13142 · Cited by 66 · see citing works
Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia
Beltrán-Camacho, L., Rojas-Torres, M., & Durán-Ruiz, M. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052335 · Cited by 66 · see citing works
Imanishi, Y., Hata, M., Matsukawa, R., Aoyagi, A., Omi, M., Mizutani, M., Naruse, K., Ozawa, S., Honda, M. J., Matsubara, T., et al. (2021) · Inflammation and Regeneration · doi:10.1186/s41232-021-00163-w · Cited by 65 · see citing works
Huang, Y., Lu, D., Ma, W., Liu, J., Ning, Q., Tang, F., & Long, L. (2022) · Molecular Immunology · doi:10.1016/j.molimm.2022.01.002 · Cited by 61 · see citing works
Liu, Y., & Holmes, C. A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.648098 · Cited by 58 · see citing works
Chen, W., Xie, G., Lu, Y., Wang, J., Feng, B., Wang, Q., Xu, K., & Bao, J. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121260 · Cited by 56 · see citing works
Effects of microenvironment and biological behavior on the paracrine function of stem cells
Xue, Z., Liao, Y., & Li, Y. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.03.013 · Cited by 56 · see citing works
Padinharayil, H., Varghese, J., Wilson, C. M., & George, A. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122542 · Cited by 57 · see citing works
Gholami, L., Nooshabadi, V. T., Shahabi, S., Jazaeri, M. S., Tarzemany, R., Afsartala, Z., & Khorsandi, K. (2021) · Cell & Bioscience · doi:10.1186/s13578-020-00527-8 · Cited by 56 · see citing works
Liu, S., Xu, X., Liang, S., Chen, Z., Zhang, Y., Qian, A., & Hu, L. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00619 · Cited by 51 · see citing works
Huang, B., Su, Y., Shen, E., Song, M., Liu, D., & Qi, H. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119208 · Cited by 51 · see citing works
Yuan, N., Ge, Z., Ji, W., & Li, J. (2021) · BioMed Research International · doi:10.1155/2021/6655225 · Cited by 50 · see citing works
Exosomes for angiogenesis induction in ischemic disorders
Moeinabadi‐Bidgoli, K., Rezaee, M., Hossein‐Khannazer, N., Babajani, A., Aghdaei, H. A., Arki, M. K., Afaghi, S., Niknejad, H., & Vosough, M. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17689 · Cited by 49 · see citing works
Osteoblasts-derived exosomes regulate osteoclast differentiation through miR-503-3p/Hpse axis
Wang, Q., Shen, X., Chen, Y., Chen, J., & Li, Y. (2021) · Acta Histochemica · doi:10.1016/j.acthis.2021.151790 · Cited by 50 · see citing works
Cheng, P., Cao, T., Zhao, X., Lu, W., Miao, S., Ning, F., Wang, D., Gao, Y., Wang, L., Pei, G., et al. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.10.021 · Cited by 47 · see citing works
Sun, X., Mao, Y., Liu, B., Gu, K., Liu, H., Du, W., Li, R., & Zhang, J. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13020180 · Cited by 49 · see citing works
Brunello, G., Zanotti, F., Trentini, M., Zanolla, I., Pishavar, E., Favero, V., Favero, R., Favero, L., Bressan, E. A., Bonora, M., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050908 · Cited by 44 · see citing works
Zhu, Q., Tang, Y., Zhou, T., Yang, L., Zhang, G., Meng, Y., Zhang, H., Gao, J., Wang, C., Su, Y., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106798 · Cited by 44 · see citing works
The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
Shirazi, S., Huang, C.-C., Kang, M., Lu, Y., Ravindran, S., & Cooper, L. F. (2021) · Scientific Reports · doi:10.1038/s41598-021-85306-2 · Cited by 43 · see citing works
Exosomes: a tool for bone tissue engineering
Huber, J., Griffin, M. F., Longaker, M. T., & Quarto, N. (2022) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0246 · Cited by 41 · see citing works
Ana, I. D., Barlian, A., Hidajah, A. C., Wijaya, C. H., Notobroto, H. B., & Wungu, T. D. K. (2021) · Future Science OA · doi:10.2144/fsoa-2021-0050 · Cited by 42 · see citing works
Smolinská, V., Boháč, M., & Danišovič, Ľ. (2023) · Physiological Research · doi:10.33549/physiolres.935186 · Cited by 41 · see citing works
Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry
Miron, R. J., Estrin, N. E., Sculean, A., & Zhang, Y. (2024) · Periodontology 2000 · doi:10.1111/prd.12557 · Cited by 41 · see citing works
Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells
Zhu, M., Liu, Y., Qin, H., Tong, S., Sun, Q., Wang, T., Zhang, H., Cui, M., & Guo, S. (2020) · Cell and Tissue Banking · doi:10.1007/s10561-020-09867-8 · Cited by 40 · see citing works
Recellularization of Native Tissue Derived Acellular Scaffolds with Mesenchymal Stem Cells
Ahmed, E., Saleh, T., & Xu, M. (2021) · Cells · doi:10.3390/cells10071787 · Cited by 40 · see citing works
Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration
Macías, I., Alcorta-Sevillano, N., Infante, A., & Rodrı́guez, C. I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147724 · Cited by 40 · see citing works
Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment
Cha, K., Cho, W., Park, S., Ahn, J., Park, H., Baek, I., Lee, M., Lee, S., Arai, Y., & Lee, S. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.12.053 · Cited by 38 · see citing works
Niedermair, T., Lukas, C., Li, S., Stöckl, S., Craiovan, B. S., Brochhausen, C., Federlin, M., Herrmann, M., & Grässel, S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.615520 · Cited by 38 · see citing works
Re, F., Gabusi, E., Manferdini, C., Russo, D., & Lisignoli, G. (2021) · Biology · doi:10.3390/biology10070579 · Cited by 37 · see citing works
Wang, X., Ao, J., Lu, H., Zhao, Q., Ma, Y., Zhang, J., Ren, H., & Zhang, Y. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s248741 · Cited by 37 · see citing works
Zhao, Q., Zhang, Y., Xiao, L., Lu, H., Ma, Y., Liu, Q., & Wang, X. (2021) · Regenerative Biomaterials · doi:10.1093/rb/rbab010 · Cited by 37 · see citing works
Lu, H., Zhang, Y., Xiong, S., Zhou, Y., Xiao, L., Ma, Y., Xiao, Y., & Wang, X. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.699802 · Cited by 36 · see citing works
Clinical Development of Regenerative Medicine Targeted for Intervertebral Disc Disease
Sakai, D., Schol, J., & Watanabe, M. (2022) · Medicina · doi:10.3390/medicina58020267 · Cited by 36 · see citing works
Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy?
Baru, O., Nutu, A. M., Braicu, C., Cismaru, C. A., Berindan‐Neagoe, I., Buduru, S. D., & Badea, M. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020929 · Cited by 35 · see citing works
Cell-based therapies for rheumatoid arthritis: opportunities and challenges
Li, Y.-J., & Chen, Z. (2022) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x221100294 · Cited by 34 · see citing works
Chopra, V., Thomas, J., Kaushik, S., Rajput, S., Guha, R., Mondal, B., Naskar, S., Mandal, D., Chauhan, G., Chattopadhyay, N., et al. (2023) · Small · doi:10.1002/smll.202204637 · Cited by 35 · see citing works
Therapeutic Potential of Extracellular Vesicles in Aging and Age-Related Diseases
Sanz‐Ros, J., Mas‐Bargues, C., Romero-García, N., Huete-Acevedo, J., Dromant, M., & Borrás, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314632 · Cited by 34 · see citing works
Engineering extracellular vesicles for ROS scavenging and tissue regeneration
Dayem, A. A., Yan, E., Do, M., Kim, Y., Lee, Y., Cho, S.-G., & Kim, D.-H. (2024) · Nano Convergence · doi:10.1186/s40580-024-00430-9 · Cited by 29 · see citing works
Xu, C., Li, Z., Kang, M., Chen, Y., Sheng, R., Aghaloo, T. L., & Lee, M. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123088 · Cited by 33 · see citing works
Mesenchymal Stem Cells and Their Exocytotic Vesicles
Cai, H., & Guo, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032085 · Cited by 31 · see citing works
Extracellular vesicles: From bone development to regenerative orthopedics
Davies, O. G. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.021 · Cited by 32 · see citing works
Emerging technologies in regenerative medicine: The future of wound care and therapy
Sharma, Y., Ghatak, S., Sen, C. K., & Mohanty, S. (2024) · Journal of Molecular Medicine · doi:10.1007/s00109-024-02493-x · Cited by 32 · see citing works
Extracellular Vesicles for the Treatment of Radiation Injuries
Nanduri, L. S. Y., Duddempudi, P. K., Yang, W.-L., Tamarat, R., & Guha, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.662437 · Cited by 30 · see citing works
Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts
Novello, S., Tricot‐Doleux, S., Novella, A., Pellen‐Mussi, P., & Jeanne, S. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14040729 · Cited by 29 · see citing works
Moeinabadi‐Bidgoli, K., Rezaee, M., Rismanchi, H., Mohammadi, M. M., & Babajani, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.900418 · Cited by 32 · see citing works
Teo, K. Y. W., Tan, R., Wong, K. L., Hey, H. W. D., Hui, J. H. P., & Toh, W. S. (2023) · Cytotherapy · doi:10.1016/j.jcyt.2023.04.011 · Cited by 27 · see citing works
Application of mesenchymal stem cell-derived exosomes in kidney diseases
Deng, G., Yu, C. J., Zhu, S., Zhu, P., & Nasser, M. I. (2021) · Cellular Immunology · doi:10.1016/j.cellimm.2021.104358 · Cited by 26 · see citing works
Wu, S., Kuo, P., Rau, C., Huang, L., Lin, C.-W., Wu, Y.-C., Wu, C., Tsai, C.-W., Hsieh, T.-M., Liu, H.-T., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168877 · Cited by 26 · see citing works
Xu, Y., Huang, R., Shi, W., Zhou, R., Xie, X., Wang, M., Wang, Y., Gu, P., Ni, N., & Bi, X. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202500060 · Cited by 25 · see citing works
Immunomodulatory and Regenerative Functions of MSC-Derived Exosomes in Bone Repair
Arun, M., Rajasingh, S., Parani, M., & Rajasingh, J. (2025) · Bioengineering · doi:10.3390/bioengineering12080844 · Cited by 29 · see citing works
Mesenchymal stromal cell-derived extracellular vesicles for bone regeneration therapy
Murali, V. P., & Holmes, C. A. (2021) · Bone Reports · doi:10.1016/j.bonr.2021.101093 · Cited by 24 · see citing works
Kirkham, A. M., Bailey, A. J.-M., Tieu, A., Maganti, H. B., Montroy, J. R., Shorr, R., Campbell, T. M., Fergusson, D. A., Lalu, M. M., Elmoazzen, H., et al. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10208-9 · Cited by 23 · see citing works
Liu, F., Sun, T., An, Y., Ming, L., Li, Y., Zhou, Z., & Shang, F. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1050916 · Cited by 34 · see citing works
Ren, J., Yu, R., Xue, J., Tang, Y., Su, S., Liao, C., Guo, Q., Guo, W., & Zheng, J. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s377598 · Cited by 22 · see citing works
Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration
Lange, M., Babczyk, P., & Tobiasch, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105204 · Cited by 22 · see citing works
Li, J., Ge, Z., Ji, W., Yuan, N., & Wang, K. (2020) · BioMed Research International · doi:10.1155/2020/4176926 · Cited by 22 · see citing works
Interests of Exosomes in Bone and Periodontal Regeneration: A Systematic Review
Gegout, P., Stutz, C., Olson, J., Batool, F., Petit, C., Tenenbaum, H., Benkirane-Jessel, N., & Huck, O. (2020) · Advances in experimental medicine and biology · doi:10.1007/5584_2020_593 · Cited by 22 · see citing works
Advances in the Study of Extracellular Vesicles for Bone Regeneration
Yao, J., Liu, Y., Du, J., Xu, J., Luo, Z., Liu, Y. F., & Guo, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063480 · Cited by 22 · see citing works
Farashah, M. S. G., Mohammadi, A., Javadi, M., Rad, J. S., Shakouri, S. K., Meshgi, S., & Roshangar, L. (2023) · Cell and Tissue Banking · doi:10.1007/s10561-022-10066-w · Cited by 21 · see citing works
Emerging roles of extracellular vesicles in oral and maxillofacial areas
Wang, Q., Sun, J., Jiang, H., & Yu, M. (2025) · International Journal of Oral Science · doi:10.1038/s41368-024-00341-9 · Cited by 21 · see citing works
Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration
Shoushrah, S. H., Transfeld, J. L., Tonk, C. H., Büchner, D., Witzleben, S. T., Sieber, M. A., Schulze, M., & Tobiasch, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126387 · Cited by 21 · see citing works
Wu, H., Chen, G., Zhang, G., Lv, Q., Gu, D., & Dai, M. (2023) · Biomedical Materials · doi:10.1088/1748-605x/acb412 · Cited by 20 · see citing works
Delivery of Growth Factors to Enhance Bone Repair
Ball, J. R., Shelby, T., Hernandez, F., Mayfield, C. K., & Lieberman, J. R. (2023) · Bioengineering · doi:10.3390/bioengineering10111252 · Cited by 20 · see citing works
Chen, Z., Xue, S., Zhang, S., Cheng, K., & Ye, Q. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30274 · Cited by 20 · see citing works
Sartori, M., Graziani, G., Sassoni, E., Pagani, S., Boi, M., Maltarello, M. C., Baldini, N., & Fini, M. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112031 · Cited by 20 · see citing works
Exosomes as Neurological Nanosized Machines
Pishavar, E., Trentini, M., Zanotti, F., Camponogara, F., Tiengo, E., Zanolla, I., Bonora, M., & Zavan, B. (2022) · ACS Nanoscience Au · doi:10.1021/acsnanoscienceau.1c00062 · Cited by 19 · see citing works
Rudiansyah, M., El‐Sehrawy, A. A. M. A., Ahmad, I. S., Terefe, E. M., Abdelbasset, W. K., Bokov, D. O., Salazar, A., Rizaev, J. A., Muthanna, F. M. S., & Shalaby, M. N. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120717 · Cited by 19 · see citing works
Schol, J., Ambrosio, L., Tamagawa, S., Joyce, K., Ruiz‐Fernández, C., Nomura, A., & Sakai, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-62792-8 · Cited by 19 · see citing works
Therapeutic properties of stem cell-derived exosomes in ischemic heart disease
Raissi-Dehkordi, N., Raissi-Dehkordi, N., & Farjoo, M. H. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174839 · Cited by 19 · see citing works
Zhou, Z., Guo, C., Sun, X., Ren, Z., & Tao, J. (2023) · Stem Cells International · doi:10.1155/2023/4980871 · Cited by 18 · see citing works
Xing, X., Han, S., Ni, Y., Cheng, G., Cheng, Y., Ni, X., Deng, Y., Li, Z., & Li, Z. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121136 · Cited by 18 · see citing works
A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration
Falguera‐Uceda, M. I., Sánchez-Casanova, S., Escudero-Duch, C., & Vilaboa, N. E. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14010132 · Cited by 16 · see citing works
Niu, H. M., Gao, N., Dang, Y., Guan, Y., & Guan, J. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.03.021 · Cited by 17 · see citing works
Cataldi, A., Amoroso, R., di Giacomo, V., Zara, S., Maccallini, C., & Gallorini, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314560 · Cited by 17 · see citing works
Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases
Yang, X., Zhang, S., Lu, J., Chen, X., Zheng, T., He, R., Ye, C., & Xu, J. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1268019 · Cited by 17 · see citing works
- Authors
- Takeuchi, R., Katagiri, W., Endo, S., & Kobayashi, T.
- Affiliations
- Niigata University (JP)
- Corresponding author
- Katagiri, Wataru
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-11-21
- Volume
- 14
- Issue
- 11
- Pages
- e0225472
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6872157
- OpenAlex
- W2989744940
- Cited by
- 210
- References
- 54
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 33 · 2023: 32 · 2022: 37 · 2021: 51 · 2020: 16
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (18K09785)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- exosomes, bone marrow-derived mesenchymal stem cells, conditioned medium, bone regeneration, angiogenesis, VEGF inhibitors, osteogenic differentiation, paracrine signaling, cell transplantation, secretome
- MeSH terms
- Animals, Bone Regeneration, Cell Movement, Cells, Cultured, Disease Models, Animal, Humans, Skull, Culture Media, Conditioned, Neovascularization, Physiologic, Cell Culture Techniques, Paracrine Communication, Angiogenesis Inhibitors, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Rats, Exosomes, Mesenchymal Stem Cells
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