Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences Pub Date : 2025-01-30 DOI:10.1016/j.job.2025.100621

Tingting Xu , Yi Peng , Yanan Xu , Jing Zhu , Qiao Yang , Yali Liu , Hefeng Yang

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Abstract

Objectives

To investigate the role of small extracellular vesicles derived from induced pluripotent stem cells (iPSC-sEVs) in periodontal tissue regeneration, elucidate their potential molecular mechanisms, and provide theoretical guidance for the clinical application of iPSC-sEVs as a cell-free therapeutic strategy for periodontal tissue regeneration.

Methods

We investigated the effects of iPSC-sEVs on the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in vitro. The regenerative potential of iPSC-sEVs was evaluated in vivo, using a periodontal defect model. Bulk RNA sequencing was performed to elucidate the underlying molecular mechanisms.

Results

iPSC-sEVs were isolated, characterized, and systemically evaluated for regenerative potential. The results revealed that treatment with iPSC-sEVs significantly enhanced the proliferation, migration, and osteogenic differentiation of PDLSCs. In situ treatment with iPSC-sEVs loaded onto collagen sponges was performed in a rat model of periodontal defects. Micro-CT and histological analyses indicated that iPSC-sEV treatment markedly promoted alveolar bone repair and periodontal ligament regeneration. Mechanistically, the analysis of bulk RNA sequencing data coupled with experimental validation revealed that iPSC-sEV treatment significantly activated the mitogen-activated protein kinase (MAPK) signaling pathway in PDLSCs. Further investigation showed that the inhibition of this pathway completely abolished the proliferative effects of iPSC-sEVs on PDLSCs.

Conclusions

iPSC-sEVs promote PDLSC proliferation through MAPK signaling pathway activation, while also enhancing PDLSC migratory and osteogenic differentiation capacities, facilitates the repair and regeneration of damaged periodontal tissue and presents a potential novel therapeutic strategy for clinical periodontal tissue regeneration.

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