The Optimal Effective Dose of Adipose-Derived Stem Cell Exosomes in Wound Healing

INTRODUCTION: Although the effect of adipose-derived mesenchymal stem cell exosomes (ADSC-exos) on wound healing with different doses are shown in various studies, efficient and sufficient doses of ADSC-exos are still unknown. The study aimed to determine the optimal dose of ADSC-exos in wound healing. METHODS: The 45 Sprague-Dawley rats were randomly divided into five groups, with seven animals in each. After dorsal circular defects were created, each wound was injected as follows: group 1: saline, group 2: 10 μg/mL of ADSC-exos, group 3: 100 μg/mL of ADSC-exos, group 4: 200 μg/mL of ADSC-exos, and group 5: 400 μg/mL of ADSC-exos. The effects of ADSC-exos on epithelization, angiogenesis, and collagen formation were analyzed macroscopically, histopathologically, and immunohistochemically on day 14. RESULTS: A total of 200 μg/mL and 400 μg/mL ADSC-exos groups had higher epithelial tongue length, epithelial tongue area, and angiogenesis scores than the other groups. Although there was no statistical difference in fibrosis scores among groups, collagen fibers were becoming well-organized as the ADSC-exos doses increased. While the wound area was clinically smaller in the 200 μg/mL ADSC-exos group, there was no statistically significant difference among groups on day 14. CONCLUSIONS: A total of 200 μg/mL of ADSC-exos was found to be the adequate and effective dose for re-epithelialization and angiogenesis in cutaneous wound healing. Moreover, the collagen density increased with a more regular pattern in the 200 μg/mL group, which can be important in scar regulation.