Dental follicle stem cells can be used as a basis for regenerative cell therapy in the treatment of periodontitis, the prevalent form of gum disease, and a condition that becomes more common with age. Researchers here note that IGFBP5 expression is reduced in senescent dental follicle stem cells, and find that increased expression of IGFBP5 reduces the pace at which these cells become senescent. Cellular senescence in the cultured cells used in cell therapy is a problem that the regenerative medicine community is becoming increasingly aware of, and various efforts have been made in various contexts to try to mitigate the issue. Here, researchers employ this new knowledge regarding the role of IGFBP5 to design a better cell therapy to promote periodontal regeneration, and carry out a proof of principle study in a rat model of periodontitis.
The improvement of health and the delay of aging represent pivotal goals in medical research. Bone aging contributes to various age-related disorders, including periodontitis. Dental follicle stem cells (DFSCs) serve as ideal seed cells for periodontal regenerative therapy. Insulin-like growth factor binding protein 5 (IGFBP5) has been reported to exert complex and context-dependent effects. However, its role in DFSC senescence remains undefined. In this study, we observed a significant decrease in IGFBP5 expression in DFSCs undergoing replicative or H2O2-induced senescence.
Functional experiments demonstrated that IGFBP5 overexpression alleviated cellular senescence and enhanced osteogenic potential, a process linked to the modulation of non-canonical Wnt signaling. WNT5B was then identified as a potential downstream regulator involved in mediating the pro-osteogenic effects of IGFBP5. To translate these findings clinically, we developed Gel-vHA@oe-DFSC, a nanoparticle-embedded hydrogel system for cell delivery, which enhanced the therapeutic efficacy of DFSCs and promoted periodontal regeneration in a rat model. Collectively, our study reveals a novel function of IGFBP5 in mitigating DFSC senescence and presents a promising strategy for combating periodontal bone loss.
Link: https://doi.org/10.1038/s41368-026-00463-2
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