Research Article

Exosomes derived from human dental pulp stem cells increase flap survival with ischemia-reperfusion injuries

Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150000, PR China

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Guang Yang

https://orcid.org/0000-0002-7368-6790

Department of Oral & Maxillofacial Surgery, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province, 161000, PR China

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Ming-yue Liu

https://orcid.org/0000-0003-4253-2075

Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150000, PR China

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Meng-tong Yuan

https://orcid.org/0000-0002-2250-9970

Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150000, PR China

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Dong Wang

https://orcid.org/0000-0003-2644-2467

Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150000, PR China

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Xiao-feng Wang

*Author for correspondence:

E-mail Address: wxf_hrbmu@163.com

Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150000, PR China

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Published Online:23 Mar 2023https://doi.org/10.2217/rme-2022-0206

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Abstract

Aim: To investigate the effect of hDPSC-Exos in flap I/R injury, a condition in which tissue damage increases after blood flow is restored to the flap after ischemia. Materials & methods: HUVECs were used to investigate the influences and mechanisms of hDPSC-Exos on cell proliferation and migration. A rat model was established to verify the role of hDPSC-Exos in flap I/R injuries in vivo. Results: hDPSC-Exos promoted the proliferation, migration and tube formation of HUVECs in a dose-dependent way by activating PI3K/AKT signaling pathway, and improved the survival and microvessel density of the flap and suppressed epithelial cell apoptosis. Conclusion: hDPSC-Exos can enhance flap repair after I/R injury. This process may be mediated by the activation of PI3K/AKT signaling pathway.

Graphical abstract

Plain language summary

Skin flap transplantation is one of the most important methods of repairing refractory wounds and organ reconstruction. I/R injury and insufficiency of neovascularization significantly affect the survival of flaps. Human dental pulp stem cells (hDPSCs) are a type of mesenchymal stem cells (MSCs) present in dental pulp tissue that have attracted increasing attention. They can play a repair role in a variety of ischemic injuries and neovascularization. Exosomes are important paracrine mediators between MSCs and target cells, containing a variety of proteins, mRNA and miRNA. Recent studies have shown that some exosomes derived from MSCs can improve I/R injury, promote angiogenesis and inhibit apoptosis. This study confirmed that hDPSC-Exos could promote the proliferation, migration and tubule formation of vein endothelial cells in a dose-dependent manner. Inhibition of PI3K/AKT signaling pathway can reduce the above promoting effects, suggesting that these processes may depend on the activation of PI3K/AKT signaling pathway. In the rat model, hDPSC-Exos can significantly improve the survival rate and microvessel density of flaps, and inhibit epithelial cell apoptosis.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 4

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History

Received 6 December 2022

Accepted 9 March 2023

Published online 23 March 2023

Published in print April 2023

Information

Keywords

Author contributions

X Shi: Conceptualization, Methodology, Investigation. G Yang: Formal analysis, Data Curation. M-Y Liu: Writing - Original Draft, Writing – Review & Editing. M-T Yuan: Resources. D Wang: Visualization. X-F Wang: Validation, Supervision.

Acknowledgments

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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