Isolation methods of exosomes derived from dental stem cells
Paras Ahmad , Nathan Estrin , Nima Farshidfar , Yufeng Zhang , Richard J. Miron
International Journal of Oral Science ›› 2025, Vol. 17 ›› Issue (1) : 50
Isolation methods of exosomes derived from dental stem cells
Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities. Recently, mesenchymal stem cells have been redefined as “medical signaling cells,” with their primary biological effects mediated through exosome secretion. These exosomes, which contain lipids, proteins, RNA, and metabolites, are crucial in regulating various biological processes and enhancing regenerative therapies. Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects, low immunogenicity, excellent biocompatibility, and high drug-loading capacity. Dental stem cells, including those from apical papilla, gingiva, dental pulp, and other sources, are key contributors to exosome-mediated regenerative effects, such as tumor cell apoptosis, neuroprotection, angiogenesis, osteogenesis, and immune modulation. Despite their promise, clinical application of exosomes is limited by challenges in isolation techniques. Current methods face issues of complexity, inefficiency, and insufficient purity, hindering detailed analysis. Recent advancements, such as micro-electromechanical systems, alternating current electroosmosis, and serum-free three-dimensional cell cultures, have improved exosome isolation efficacy. This review synthesizes nearly 200 studies on dental stem cell-derived exosomes, highlighting their potential in treating a wide range of conditions, including periodontal diseases, cancer, neurodegenerative disorders, diabetes, and more. Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.
| [1] |
|
| [2] |
|
| [3] |
|
| [4] |
|
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
|
| [9] |
|
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
|
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
|
| [27] |
|
| [28] |
|
| [29] |
|
| [30] |
|
| [31] |
|
| [32] |
|
| [33] |
|
| [34] |
|
| [35] |
|
| [36] |
|
| [37] |
|
| [38] |
|
| [39] |
|
| [40] |
|
| [41] |
|
| [42] |
|
| [43] |
|
| [44] |
|
| [45] |
|
| [46] |
|
| [47] |
|
| [48] |
|
| [49] |
|
| [50] |
|
| [51] |
|
| [52] |
|
| [53] |
|
| [54] |
|
| [55] |
|
| [56] |
|
| [57] |
|
| [58] |
|
| [59] |
|
| [60] |
|
| [61] |
|
| [62] |
|
| [63] |
|
| [64] |
|
| [65] |
|
| [66] |
|
| [67] |
|
| [68] |
|
| [69] |
|
| [70] |
|
| [71] |
|
| [72] |
|
| [73] |
|
| [74] |
|
| [75] |
|
| [76] |
|
| [77] |
|
| [78] |
Gratpain, V. et al. Influence of a pro-inflammatory stimulus on the miRNA and lipid content of human dental stem cell-derived extracellular vesicles and their impact on microglial activation. Heliyon 10 (2024). |
| [79] |
|
| [80] |
|
| [81] |
Liang, L. et al. High-yield nanovesicles extruded from dental follicle stem cells promote the regeneration of periodontal tissues as an alternative of exosomes. J. Clin. Periodontol. 51, 1395–1407 (2024). |
| [82] |
Huang, Y. et al. Lipopolysaccharide-preconditioned dental follicle stem cells derived small extracellular vesicles treating periodontitis via reactive oxygen species/mitogen-activated protein kinase signaling-mediated antioxidant effect. Int. J. Nanomed. 17, 799–819 (2022). |
| [83] |
|
| [84] |
|
| [85] |
|
| [86] |
|
| [87] |
|
| [88] |
|
| [89] |
|
| [90] |
|
| [91] |
|
| [92] |
|
| [93] |
|
| [94] |
|
| [95] |
|
| [96] |
|
| [97] |
|
| [98] |
|
| [99] |
|
| [100] |
|
| [101] |
Chen, J. et al. miRNA-148a–containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model. JCI Insight 9 (2024). |
| [102] |
|
| [103] |
|
| [104] |
|
| [105] |
|
| [106] |
|
| [107] |
|
| [108] |
|
| [109] |
|
| [110] |
|
| [111] |
|
| [112] |
|
| [113] |
|
| [114] |
|
| [115] |
|
| [116] |
|
| [117] |
Yu, T., Mi, N., Song, Y. & Xie, W. Exosomes miR-92a-3p from human exfoliated deciduous teeth inhibits periodontitis progression via the KLF4/PI3K/AKT pathway. J. Periodontal Res. 59, 771–782 (2024). |
| [118] |
|
| [119] |
Jing, Y. et al. Apoptotic vesicles modulate endothelial metabolism and ameliorate ischemic retinopathy via PD1/PDL1 Axis. Adv. Healthc. Mater. 13, e2303527 (2024). |
| [120] |
|
| [121] |
|
| [122] |
|
| [123] |
|
| [124] |
|
| [125] |
|
| [126] |
|
| [127] |
|
| [128] |
|
| [129] |
|
| [130] |
|
| [131] |
|
| [132] |
|
| [133] |
|
| [134] |
|
| [135] |
|
| [136] |
|
| [137] |
|
| [138] |
|
| [139] |
|
| [140] |
|
| [141] |
|
| [142] |
|
| [143] |
|
| [144] |
Huang, X. et al. Odontogenesis-empowered extracellular vesicles safeguard donor-recipient stem cell interplay to support tooth regeneration. Small 20, e2400260 (2024). |
| [145] |
|
| [146] |
|
| [147] |
|
| [148] |
Diomede, F. et al. A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells. Int. J. Nanomed. 13, 3805–3825 (2018). |
| [149] |
|
| [150] |
|
| [151] |
|
| [152] |
Niu, Q. et al. FoxO1-overexpressed small extracellular vesicles derived from hPDLSCs promote periodontal tissue regeneration by reducing mitochondrial dysfunction to regulate osteogenesis and inflammation. Int. J. Nanomed. 19, 8751–8768 (2024). |
| [153] |
|
| [154] |
|
| [155] |
|
| [156] |
|
| [157] |
Zhao, B. et al. Periodontal ligament stem cell-derived small extracellular vesicles embedded in matrigel enhance bone repair through the adenosine receptor signaling pathway. Int. J. Nanomed. 17, 519-536. |
| [158] |
Lu, J., Yu, N., Liu, Q., Xie, Y. & Zhen, L. Periodontal ligament stem cell exosomes key to regulate periodontal regeneration by miR-31-5p in mice model. Int. J. Nanomed. 18, 5327–5342 (2023). |
| [159] |
|
| [160] |
|
| [161] |
|
| [162] |
|
| [163] |
|
| [164] |
|
| [165] |
|
| [166] |
|
| [167] |
|
| [168] |
|
| [169] |
|
| [170] |
|
| [171] |
|
| [172] |
|
| [173] |
|
| [174] |
|
| [175] |
|
| [176] |
|
| [177] |
|
| [178] |
|
| [179] |
|
| [180] |
|
| [181] |
|
| [182] |
|
| [183] |
|
| [184] |
|
| [185] |
|
| [186] |
|
| [187] |
|
| [188] |
|
| [189] |
|
| [190] |
|
| [191] |
|
| [192] |
|
| [193] |
|
| [194] |
|
| [195] |
|
| [196] |
Lin, T.-Y. et al. 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucoside–stimulated dental pulp stem cells-derived exosomes for wound healing and bone regeneration. J. Dental Sci. 20, 154–163 (2024). |
| [197] |
|
| [198] |
|
| [199] |
|
| [200] |
|
| [201] |
|
| [202] |
|
| [203] |
Fei, Y., Ling, Z., Tong, Q.& Wang, J. Apoptotic extracellular vesicles from supernumerary tooth-derived pulp stem cells transfer COL1A1 to promote angiogenesis via PI3K/Akt/VEGF pathway. Int. J. Nanomed. 19, 6811–6828 (2024). |
| [204] |
|
| [205] |
|
| [206] |
|
| [207] |
|
| [208] |
|
| [209] |
|
| [210] |
|
| [211] |
|
| [212] |
|
| [213] |
|
| [214] |
|
| [215] |
|
| [216] |
|
| [217] |
|
| [218] |
Altanerova, U. et al. Human mesenchymal stem cell-derived iron oxide exosomes allow targeted ablation of tumor cells via magnetic hyperthermia. Int. J. Nanomed. 12, 7923–7936 (2017). |
| [219] |
|
| [220] |
|
| [221] |
|
| [222] |
|
| [223] |
|
| [224] |
|
| [225] |
Teixeira, M. R., Alievi, A. L., da Costa, V. R., Kerkis, I. & Araldi, R. P. Exploring the therapeutic potential of extracellular vesicles derived from human immature dental pulp cells on papillary thyroid cancer. Int. J. Mol. Sci. 25, 8178 (2024). |
| [226] |
Chen, Y. et al. The application of pulp tissue derived-exosomes in pulp regeneration: a novel cell-homing approach. Int. J. Nanomed. 17, 465-476 (2022). |
| [227] |
|
| [228] |
|
| [229] |
|
| [230] |
|
| [231] |
|
| [232] |
|
| [233] |
|
| [234] |
|
| [235] |
|
| [236] |
Chai, Y. et al. Study on the role and mechanism of exosomes derived from dental pulp stem cells in promoting regeneration of myelin sheath in rats with sciatic nerve injury. Mol. Neurobiol. 61, 6175–6188 (2024). |
| [237] |
|
| [238] |
|
| [239] |
|
| [240] |
|
| [241] |
|
| [242] |
|
| [243] |
|
| [244] |
|
| [245] |
|
| [246] |
|
| [247] |
|
| [248] |
|
| [249] |
|
| [250] |
|
| [251] |
|
| [252] |
|
| [253] |
|
| [254] |
|
| [255] |
|
| [256] |
|
| [257] |
|
| [258] |
|
| [259] |
|
| [260] |
|
| [261] |
|
| [262] |
|
| [263] |
|
| [264] |
|
| [265] |
|
| [266] |
|
| [267] |
|
| [268] |
|
| [269] |
|
| [270] |
|
| [271] |
|
| [272] |
|
| [273] |
|
| [274] |
|
| [275] |
|
| [276] |
|
| [277] |
|
| [278] |
|
| [279] |
|
| [280] |
|
| [281] |
|
| [282] |
|
| [283] |
|
| [284] |
|
| [285] |
|
| [286] |
|
| [287] |
|
| [288] |
|
| [289] |
|
| [290] |
|
| [291] |
|
| [292] |
|
| [293] |
|
| [294] |
|
| [295] |
|
| [296] |
|
| [297] |
|
| [298] |
|
| [299] |
|
| [300] |
|
| [301] |
|
| [302] |
|
| [303] |
|
| [304] |
|
| [305] |
|
| [306] |
|
| [307] |
Mukherjee, S. & Sarkar, K. Lateral migration of a viscoelastic drop in a Newtonian fluid in a shear flow near a wall. Phys. Fluids 26 (2014). |
| [308] |
|
| [309] |
|
| [310] |
Jiang D., Ni C., Tang W., Huang D., Xiang N. Inertial microfluidics in contraction–expansion microchannels: a review. Biomicrofluidics 15 (2021). |
| [311] |
|
| [312] |
|
| [313] |
Bowman T. J., Drazer G., Frechette J. Inertia and scaling in deterministic lateral displacement. Biomicrofluidics 7 (2013). |
| [314] |
|
| [315] |
|
| [316] |
|
| [317] |
|
| [318] |
|
| [319] |
|
| [320] |
|
| [321] |
|
| [322] |
|
| [323] |
|
| [324] |
Chiriacò, M. S. et al. Lab-on-chip for exosomes and microvesicles detection and characterization. Sensors 18, 3175 (2018). |
| [325] |
|
| [326] |
Sunahiro, S., Senaha, M., Yamada, M. & Seki, M., editors. Pinched Flow Fractionization device for sizes and density dependent separation of particles utilizing centrifugal pumping. In: 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences, San Diego, California, USA (2008). |
| [327] |
|
| [328] |
|
| [329] |
|
| [330] |
|
| [331] |
|
| [332] |
|
| [333] |
|
| [334] |
|
| [335] |
|
| [336] |
|
| [337] |
|
| [338] |
Díaz-Reinoso, B. Concentration and Purification of Seaweed Extracts Using Membrane Technologies. Sustainable Seaweed Technologies 371–390 (Elsevier, 2020). |
| [339] |
|
| [340] |
|
| [341] |
|
| [342] |
|
| [343] |
|
| [344] |
|
| [345] |
|
| [346] |
|
| [347] |
|
| [348] |
|
| [349] |
|
| [350] |
|
| [351] |
|
| [352] |
|
| [353] |
|
| [354] |
|
| [355] |
|
| [356] |
|
| [357] |
|
| [358] |
|
| [359] |
|
| [360] |
|
| [361] |
Yeo, J. C. et al. Label-free extraction of extracellular vesicles using centrifugal microfluidics. Biomicrofluidics 12 (2018). |
| [362] |
|
| [363] |
Zhang, Y. et al. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. Int. J. Nanomed. 15, 6917-6934 (2020). |
| [364] |
|
| [365] |
|
| [366] |
|
| [367] |
|
| [368] |
|
| [369] |
|
| [370] |
|
| [371] |
|
| [372] |
|
| [373] |
|
| [374] |
|
| [375] |
|
The Author(s)
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