Journal article
Extracellular Vesicles-Induced Cell Homing and Odontogenesis via microRNA Signaling for Dentin Regeneration
International journal of molecular sciences, Vol.26(15), 7182
07/25/2025
DOI: 10.3390/ijms26157182
PMCID: PMC12346742
PMID: 40806315
Abstract
Reparative tertiary dentinogenesis requires the recruitment and odontogenic differentiation of dental pulp stem cells (DPSCs). Extracellular vesicles (EVs) as bioactive molecules have gained attention in regenerative medicine for their ability to mediate tissue repair through intercellular communication, influencing cell recruitment, proliferation, and differentiation. This study aimed to evaluate the effects of EVs on DPSC homing and odontogenic differentiation for dentin regeneration. DPSC-derived EVs were cultured in either growth (EV-G) or odontogenic differentiation (EV-O) conditions and isolated using a modified precipitation method. EVs were characterized by nanoparticle tracking analysis, scanning electron microscopy, antibody array, and cellular uptake assay. Treatment with 5 × 108 EVs/mL significantly enhanced DPSC chemotaxis and proliferation compared with a no-treatment control and a lower dosage of EV (5 × 107 EVs/mL). Gene expression and biochemical analyses revealed that EV-O up-regulated odontogenic markers including collagen type 1A1 (COL1A1), runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALP). EV-O enhanced dentin regeneration by approximately 55% over vehicle controls in a rabbit partial dentinotomy/pulpotomy model. We identified key microRNAs (miR-21-5p, miR-221-3p, and miR-708-3p) in EV-O involved in cell homing and odontogenesis. In conclusion, our EV-based cell homing and odontogenic differentiation strategy has significant therapeutic potential for dentin regeneration.
Details
- Title: Subtitle
- Extracellular Vesicles-Induced Cell Homing and Odontogenesis via microRNA Signaling for Dentin Regeneration
- Creators
- Venkateswaran Ganesh - University of IowaDouglas C. Fredericks - University of IowaEmily B. Petersen - University of IowaHenry L. Keen - University of IowaRui He - University of IowaJordon D. TurnerJames A. Martin - University of IowaAliasger K. Salem - University of IowaKyungsup Shin - University of Iowa, OrthodonticsAbhishek Parolia - University of IowaDongrim Seol - University of Iowa
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.26(15), 7182
- DOI
- 10.3390/ijms26157182
- PMID
- 40806315
- PMCID
- PMC12346742
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Publisher
- MDPI
- Grant note
- National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health (NIH)
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This manuscript is the result of funding in whole or in part by the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health (NIH) under Award Number R03DE030515. It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given a right to make this manuscript publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
- Language
- English
- Date published
- 07/25/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Research Administration; Endodontics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Iowa Institute of Human Genetics
- Record Identifier
- 9984927082802771
Metrics
10 Record Views