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BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Bone Defect | Research

Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis

Authors: Huan Zhou, Yan-Xin Qi, Chun-Hui Zhu, Ang Li, Dan-Dan Pei

Published in: BMC Oral Health | Issue 1/2023

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Abstract

Background

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models of periodontitis.

Methods

The PubMed, Web of Science, and Embase electronic databases were searched up to Dec 2022 to retrieve preclinical studies examining the use of MSC-EVs for periodontitis treatment. Meta-analyses and sub-group analyses were performed to assess the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) or the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) in pre-clinical animal models of periodontitis.

Results

11 studies published from Mar 2019 to Oct 2022 met the inclusion criteria. Overall, MSC-EVs contributed to periodontal bone regeneration in the inflammatory bone loss area due to periodontitis, as represented by a weighted mean difference (WMD) of 14.07% (95% CI = 6.73, 21.41%, p < 0.001) for BV/TV and a WMD of -0.12 mm (95% CI= -0.14, -0.11 mm, p < 0.001) for CEJ-ABC. However, sub-analysis suggested that there was no significant difference in CEJ-ABC between studies with bioactive scaffolds and studies without bioactive scaffolds (p = 0.60).

Conclusions

The present study suggests that MSC-EVs may represent an attractive therapy for the treatment of inflammatory bone loss within periodontitis.
Appendix
Available only for authorised users
Literature
1.
Li H, Deng Y, Tan M, Feng G, Kuang Y, Li J, Song J. Low-intensity pulsed ultrasound upregulates osteogenesis under inflammatory conditions in periodontal ligament stem cells through unfolded protein response. Stem Cell Res Ther. 2020;11(1):215.PubMedPubMedCentral
2.
Yan W, Cao Y, Yang H, Han N, Zhu X, Fan Z, Du J, Zhang F. CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment. Cell Prolif. 2019;52(6):e12691.PubMedPubMedCentral
3.
Peres MA, Macpherson LMD, Weyant RJ, Daly B, Venturelli R, Mathur MR, Listl S, Celeste RK, Guarnizo-Herreño CC, Kearns C, Benzian H, Allison P, Watt RG. Oral diseases: a global public health challenge. Lancet. 2019;394(10194):249–60.PubMed
4.
Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, Nguyen M, Haditsch U, Raha D, Griffin C, Holsinger LJ, Arastu-Kapur S, Kaba S, Lee A, Ryder MI, Potempa B, Mydel P, Hellvard A, Adamowicz K, Hasturk H, Walker GD, Reynolds EC, Faull RLM, Curtis MA, Dragunow M, Potempa J. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.PubMedPubMedCentral
5.
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038.PubMed
6.
Li G, Han N, Yang H, Zhang X, Cao Y, Cao Y, Shi R, Wang S, Fan Z. SFRP2 promotes stem cells from apical papilla-mediated periodontal tissue regeneration in miniature pig. J Oral Rehabil. 2020;47(Suppl 1):12–8.PubMed
7.
Han N, Zhang F, Li G, Zhang X, Lin X, Yang H, Wang L, Cao Y, Du J, Fan Z. Local application of IGFBP5 protein enhanced periodontal tissue regeneration via increasing the migration, cell proliferation and osteo/dentinogenic differentiation of mesenchymal stem cells in an inflammatory niche. Stem Cell Res Ther. 2017;8(1):210.PubMedPubMedCentral
8.
Lei F, Li M, Lin T, Zhou H, Wang F, Su X. Treatment of inflammatory bone loss in periodontitis by stem cell-derived exosomes. Acta Biomater. 2022;141:333–43.PubMed
9.
Zhao Y, Shi Y, Yang H, Liu M, Shen L, Zhang S, Liu Y, Zhu J, Lan J, Li J, Ge S. Stem cell microencapsulation maintains stemness in inflammatory microenvironment. Int J Oral Sci. 2022;14(1):48.PubMedPubMedCentral
10.
Phinney DG, Pittenger MF. Concise Review: MSC-Derived Exosomes for cell-free therapy. Stem Cells. 2017;35(4):851–8.PubMed
11.
Li W, Liu Y, Zhang P, Tang Y, Zhou M, Jiang W, Zhang X, Wu G, Zhou Y. Tissue-Engineered Bone immobilized with human adipose stem cells-derived Exosomes promotes bone regeneration. ACS Appl Mater Interfaces. 2018;10(6):5240–54.PubMed
12.
Chew JRJ, Chuah SJ, Teo KYW, Zhang S, Lai RC, Fu JH, Lim LP, Lim SK, Toh WS. Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomater. 2019;89:252–64.PubMed
13.
Zhao Y, Gong Y, Liu X, He J, Zheng B, Liu Y. The experimental study of Periodontal ligament stem cells derived Exosomes with Hydrogel accelerating bone regeneration on alveolar bone defect. Pharmaceutics. 2022;14(10):2189.PubMedPubMedCentral
14.
Murphy DE, de Jong OG, Brouwer M, Wood MJ, Lavieu G, Schiffelers RM, Vader P. Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking. Exp Mol Med. 2019;51(3):1–12.PubMed
15.
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977.PubMedPubMedCentral
16.
Su L, Li R, Zhang Z, Liu J, Du J, Wei H. Identification of altered exosomal microRNAs and mRNAs in Alzheimer’s disease. Ageing Res Rev. 2022;73:101497.PubMed
17.
Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R. The current landscape of the mesenchymal stromal cell secretome: a new paradigm for cell-free regeneration. Cytotherapy. 2016;18(1):13–24.PubMed
18.
Zhang ZG, Buller B, Chopp M. Exosomes - beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol. 2019;15(4):193–203.PubMed
19.
Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021;20(5):362–83.PubMed
20.
Jeyaram A, Jay SM. Preservation and Storage Stability of Extracellular vesicles for therapeutic applications. AAPS J. 2017;20(1):1.PubMed
21.
Wang M, Li J, Ye Y, Chen D, Song J. SHED-derived exosomes improve the repair capacity and osteogenesis potential of hPDLCs. Oral Dis. 2022 Feb 13.
22.
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14:43.PubMedPubMedCentral
23.
Cui J, Jin L, Ding M, He J, Yang L, Cui S, Wang X, Ma J, Liu A. Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis. Stem Cell Res Ther. 2022;13(1):118.PubMedPubMedCentral
24.
Petrosyan A, Martins PN, Solez K, Uygun BE, Gorantla VS, Orlando G. Regenerative medicine applications: an overview of clinical trials. Front Bioeng Biotechnol. 2022;10:942750.PubMedPubMedCentral
25.
Shimizu Y, Takeda-Kawaguchi T, Kuroda I, Hotta Y, Kawasaki H, Hariyama T, Shibata T, Akao Y, Kunisada T, Tatsumi J, Tezuka KI. Exosomes from dental pulp cells attenuate bone loss in mouse experimental periodontitis. J Periodontal Res. 2022;57(1):162–72.PubMed
26.
Kirkham AM, Bailey AJM, Tieu A, Maganti HB, Montroy J, Shorr R, Campbell TM, Fergusson DA, Lalu MM, Elmoazzen H, Allan DS. MSC-Derived Extracellular Vesicles in Preclinical Animal Models of Bone Injury: a systematic review and Meta-analysis. Stem Cell Rev Rep. 2022;18(3):1054–66.PubMed
27.
Wang J, Zhu M, Hu Y, Chen R, Hao Z, Wang Y, Li J. Exosome-hydrogel system in bone tissue Engineering: a promising therapeutic strategy. Macromol Biosci 2022 Dec 27:e2200496.
28.
Wang D, Cao H, Hua W, Gao L, Yuan Y, Zhou X, Zeng Z. Mesenchymal stem cell-derived extracellular vesicles for bone defect repair. Membr (Basel). 2022;12(7):716.
29.
Yan HC, Yu TT, Li J, Qiao YQ, Wang LC, Zhang T, Li Q, Zhou YH, Liu DW. The delivery of Extracellular vesicles loaded in Biomaterial Scaffolds for Bone Regeneration. Front Bioeng Biotechnol. 2020;8:1015.PubMedPubMedCentral
30.
Pinheiro A, Silva AM, Teixeira JH, Gonçalves RM, Almeida MI, Barbosa MA, Santos SG. Extracellular vesicles: intelligent delivery strategies for therapeutic applications. J Control Release. 2018;289:56–69.PubMed
31.
Lu Y, Yang Y, Liu S, Ge S. Biomaterials constructed for MSC-derived extracellular vesicle loading and delivery-a promising method for tissue regeneration. Front Cell Dev Biol. 2022;10:898394.PubMedPubMedCentral
32.
Yu M, Gu G, Cong M, Du M, Wang W, Shen M, Zhang Q, Shi H, Gu X, Ding F. Repair of peripheral nerve defects by nerve grafts incorporated with extracellular vesicles from skin-derived precursor Schwann cells. Acta Biomater. 2021;134:190–203.PubMed
33.
Gangadaran P, Rajendran RL, Lee HW, Kalimuthu S, Hong CM, Jeong SY, Lee SW, Lee J, Ahn BC. Extracellular vesicles from mesenchymal stem cells activates VEGF receptors and accelerates recovery of hindlimb ischemia. J Control Release. 2017;264:112–26.PubMed
34.
Wu J, Chen L, Wang R, Song Z, Shen Z, Zhao Y, Huang S, Lin Z. Exosomes secreted by stem cells from human exfoliated deciduous Teeth promote alveolar bone defect repair through the regulation of Angiogenesis and Osteogenesis. ACS Biomater Sci Eng. 2019;5(7):3561–71.PubMed
35.
Ying C, Wang R, Wang Z, Tao J, Yin W, Zhang J, Yi C, Qi X, Han D. BMSC-Exosomes carry mutant HIF-1α for improving angiogenesis and osteogenesis in critical-sized calvarial defects. Front Bioeng Biotechnol. 2020;8:565561.PubMedPubMedCentral
36.
Del Suárez-López F, Monje A. Efficacy of biologics for alveolar ridge preservation/reconstruction and implant site development: an American Academy of Periodontology best evidence systematic review. J Periodontol. 2022;93(12):1827–47.
37.
Ma L, Rao N, Jiang H, Dai Y, Yang S, Yang H, Hu J. Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration. Stem Cell Res Ther. 2022;13(1):92.PubMedPubMedCentral
38.
Shi W, Guo S, Liu L, Liu Q, Huo F, Ding Y, Tian W. Small extracellular vesicles from Lipopolysaccharide-Preconditioned Dental follicle cells promote Periodontal Regeneration in an inflammatory microenvironment. ACS Biomater Sci Eng. 2020;6(10):5797–810.PubMed
39.
Nakao Y, Fukuda T, Zhang Q, Sanui T, Shinjo T, Kou X, Chen C, Liu D, Watanabe Y, Hayashi C, Yamato H, Yotsumoto K, Tanaka U, Taketomi T, Uchiumi T, Le AD, Shi S, Nishimura F. Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater. 2021;122:306–24.PubMed
40.
Zhang Y, Chen J, Fu H, Kuang S, He F, Zhang M, Shen Z, Qin W, Lin Z, Huang S. Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium. Int J Oral Sci. 2021;13(1):43.PubMedPubMedCentral
41.
Liu L, Guo S, Shi W, Liu Q, Huo F, Wu Y, Tian W. Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote Periodontal Regeneration. Tissue Eng Part A. 2021;27(13–14):962–76.PubMed
42.
Shen Z, Kuang S, Zhang Y, Yang M, Qin W, Shi X, Lin Z. Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism. Bioact Mater. 2020;5(4):1113–26.PubMedPubMedCentral
43.
Wei J, Song Y, Du Z, Yu F, Zhang Y, Jiang N, Ge X. Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis. J Mol Histol. 2020;51(4):455–66.PubMed
44.
Hayrapetyan A, Jansen JA, van den Beucken JJ. Signaling pathways involved in osteogenesis and their application for bone regenerative medicine. Tissue Eng Part B Rev. 2015;21(1):75–87.PubMed
45.
Tréton G, Sayer C, Schürz M, Jaritsch M, Mueller A, Matea CT, Stanojlovic V, Melo-Benirschke H, Be C, Krembel C, Rodde S, Haffke M, Hintermann S, Marzinzik A, Ripoche S, Blöchl C, Hollerweger J, Auer D, Cabrele C, Huber CG, Hintersteiner M, Wagner T, Lingel A, Meisner-Kober N. Quantitative and functional characterisation of extracellular vesicles after passive loading with hydrophobic or cholesterol-tagged small molecules. J Control Release. 2023 Aug 9:S0168-3659(23)00506-0.
46.
Li Q, Fu X, Kou Y, Han N. Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue. Theranostics. 2023;13(12):4266–86.PubMedPubMedCentral
Metadata
Title
Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis
Authors
Huan Zhou
Yan-Xin Qi
Chun-Hui Zhu
Ang Li
Dan-Dan Pei
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Bone Defect
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03398-w

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