Lipoaspirate fluid derived factors and extracellular vesicles accelerate wound healing in a rat burn model

Yue Wu; Pengyu Hong; Pan Liu; Qi Zhang; Yue Zhang; Baohua Yang; Huixing Liu; Lei Liu; Weidong Tian; Mei Yu

doi:10.3389/fbioe.2023.1185251

Lipoaspirate fluid derived factors and extracellular vesicles accelerate wound healing in a rat burn model

Front Bioeng Biotechnol. 2023 Jun 22:11:1185251. doi: 10.3389/fbioe.2023.1185251. eCollection 2023.

Authors

Yue Wu^{1

2

3}, Pengyu Hong^{1

2

3}, Pan Liu^{1

2

3}, Qi Zhang^{1

2

3}, Yue Zhang^{1

2

3}, Baohua Yang^{1

2

3}, Huixing Liu⁴, Lei Liu^{1

2

3}, Weidong Tian^{1

2

3}, Mei Yu^{1

2}

Affiliations

¹ State Key Laboratory of Oral Disease, National Engineering Laboratory for Oral Regenerative Medicine, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
² Engineering Research Center of Oral Translational Medicine, Ministry of Education, Sichuan University, Chengdu, China.
³ Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
⁴ Sichuan Huamel Zixin Medical Aesthetic Hospital, Chengdu, Sichuan, China.

Abstract

Background: The regenerative capabilities of derivatives derived from the fat layer of lipoaspirate have been demonstrated. However, the large volume of lipoaspirate fluid has not attracted extensive attention in clinical applications. In this study, we aimed to isolate the factors and extracellular vesicles from human lipoaspirate fluid and evaluate their potential therapeutic efficacy. Methods: Lipoaspirate fluid derived factors and extracellular vesicles (LF-FVs) were prepared from human lipoaspirate and characterized by nanoparticle tracking analysis, size-exclusion chromatography and adipokine antibody arrays. The therapeutic potential of LF-FVs was evaluated on fibroblasts in vitro and rat burn model in vivo. Wound healing process was recorded on days 2, 4, 8, 10, 12 and 16 post-treatment. The scar formation was analyzed by histology, immunofluorescent staining and scar-related gene expression at day 35 post-treatment. Results: The results of nanoparticle tracking analysis and size-exclusion chromatography indicated that LF-FVs were enriched with proteins and extracellular vesicles. Specific adipokines (adiponectin and IGF-1) were detected in LF-FVs. In vitro, LF-FVs augmented the proliferation and migration of fibroblasts in a dose-dependent manner. In vivo, the results showed that LF-FVs significantly accelerated burn wound healing. Moreover, LF-FVs improved the quality of wound healing, including regenerating cutaneous appendages (hair follicles and sebaceous glands) and decreasing scar formation in the healed skin. Conclusion: LF-FVs were successfully prepared from lipoaspirate liquid, which were cell-free and enriched with extracellular vesicles. Additionally, they were found to improve wound healing in a rat burn model, suggesting that LF-FVs could be potentially used for wound regeneration in clinical settings.

Keywords: adipokines; extracellular vesicles; lipoaspirate fluid; rat burn model; wound healing.

Grants and funding

This work was supported by National Natural Science Foundation of China (U21A20369 and 81670951), Key Technology R&D Program of Sichuan Province (2019YFS0312) and Applied Basic Research Project of Sichuan Province (2020YJ0278).