Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2023; 15(9): 947-959
Published online Sep 26, 2023. doi: 10.4252/wjsc.v15.i9.947
Enhanced wound healing and hemostasis with exosome-loaded gelatin sponges from human umbilical cord mesenchymal stem cells
Xin-Mei Hu, Can-Can Wang, Yu Xiao, Peng Jiang, Yu Liu, Zhong-Quan Qi
Xin-Mei Hu, Can-Can Wang, Yu Xiao, Peng Jiang, Yu Liu, Zhong-Quan Qi, Medical College, Guangxi University, Nanning 530004, Guangxi Zhuang Autonomous Region, China
Author contributions: Qi ZQ and Hu XM contributed to the study conception and design; Hu XM, Wang CC, and Xiao Y contributed to data collection, analysis, and interpretation; Hu XM contributed to manuscript writing; Hu XM, Wang CC, Xiao Y, Jiang P, and Liu Y performed the animal experiments; Qi ZQ, Hu XM, and Xiao Y contributed to the conception, design, financial support, and final approval of the manuscript; and all the authors have read and approved the final manuscript.
Supported by the National Key R&D Program of China, No. 2018YFA0108304; the National Natural Science Foundation of China, No. 81771721 and 81971505; and the Innovation Project of Guangxi Graduate Education, No. YCBZ2022004 and YCBZ2022045.
Institutional animal care and use committee statement: All of the experimental procedures involving animals were reviewed and approved by the Ethics Committee of Guangxi University, Nanning, China (No. GXU-2021-1000).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhong-Quan Qi, MD, PhD, Professor, Medical College, Guangxi University, No. 100 Daxuedong Road, Nanning 530004, Guangxi Zhuang Autonomous Region, China. yxyyz@gxu.edu.cn
Received: August 14, 2023
Peer-review started: August 14, 2023
First decision: August 22, 2023
Revised: August 31, 2023
Accepted: September 14, 2023
Article in press: September 14, 2023
Published online: September 26, 2023
Abstract
BACKGROUND

Rapid wound healing remains a pressing clinical challenge, necessitating studies to hasten this process. A promising approach involves the utilization of human umbilical cord mesenchymal stem cells (hUC-MSCs) derived exosomes. The hypothesis of this study was that these exosomes, when loaded onto a gelatin sponge, a common hemostatic material, would enhance hemostasis and accelerate wound healing.

AIM

To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.

METHODS

Ultracentrifugation was used to extract exosomes from hUC-MSCs. Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot techniques were used to validate the exosomes. In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival. New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions. Hemolysis test was conducted using a 2% rabbit red blood cell suspension to detect whether they caused hemolysis. Moreover, in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley (SD) rats to perform biocompatibility tests. In addition, coagulation index test was conducted to evaluate their impact on blood coagulation. Meanwhile, SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.

RESULTS

The NTA, TEM, and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs. The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity, skin irritation, or hemolysis, and they demonstrated good compatibility in SD rats. Additionally, the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated. The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge, and they showed excellent hemostatic performance in a liver defect hemostasis model. Finally, the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.

CONCLUSION

Collectively, the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing, warranting further clinical application.

Keywords: Human umbilical cord mesenchymal stem cells, Exosomes, Gelatin sponge, Safety, Hemostasis, Wound healing

Core Tip: In this study, we loaded exosomes derived from human umbilical cord mesenchymal stem cells onto a gelatin sponge, a common hemostatic substance in clinics, to stop bleeding and promote wound healing. The fabricated material appears relatively safe, provides better hemostatic activity than gelatin sponge alone, and promotes good wound healing.