Human mesenchymal stromal cell-derived exosomes promote wound healing in a mouse model of radiation-induced injury

Background: Mesenchymal stromal cells (MSCs) have been reported to promote tissue regeneration in numerous pre-clinical animal models, including radiation burns. MSC-derived exosomes (MSC-EXO) might be a main paracrine mechanism for these cells to mediate their therapeutic effect. Recent studies hav...

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Bibliographic Details
Published in:Journal of extracellular vesicles 2018-01, Vol.7, p.250-250
Main Authors: Ribault, Alexandre, Loinard, Céline, Flamant, Stephane, Lim, Sai Kiang, Tamarat, Radia
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animal models
Blood levels
Bone marrow
Doppler effect
Endothelial cells
Exosomes
Flow cytometry
Inflammation
Injection
Leukocyte migration
Mesenchyme
Monocytes
Paracrine signalling
Perfusion
Regeneration
Rodents
SDF-1 protein
Skeletal muscle
Skin
Spleen
Vascular endothelial growth factor
Wound healing
X-rays
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Summary:Background: Mesenchymal stromal cells (MSCs) have been reported to promote tissue regeneration in numerous pre-clinical animal models, including radiation burns. MSC-derived exosomes (MSC-EXO) might be a main paracrine mechanism for these cells to mediate their therapeutic effect. Recent studies have shown that MSC-EXO could exert regenerative functions in several tissues, including skin and skeletal muscle. We hypothesized that MSC-EXO could participate to the wound healing process of radio-induced injury in mice. Methods: Mice lower limb was exposed to 80 Gy X-ray irradiation to induce radiation injury. After 14 days, mice received an intramuscular injection of 106 human MSCs, 400 ^g MSC-EXO or PBS. Animals were monitored weekly to establish an injury score based on the assessment of wound extent, ulceration, moist desquamation and limb retraction. Skin perfusion was evaluated by laser Doppler imaging. Mice were sacrificed at several time points, and tissues of both irradiated and contralateral limbs were harvested for histological and biochemical analyses. Bone marrow, spleen and blood were collected for analysis of inflammatory cells and circulating factors. Results: MSC-EXO decreased the injury score at 7 and 14 days postinjection, compared to MSC and PBS groups, suggesting that MSC-EXO promote wound healing in a preventive manner. Irradiation increased skin perfusion in PBS-injected animals, while MSC-EXO and MSCs restored skin perfusion to levels similar to non-irradiated legs. Moreover, we found that MSC-EXO increased blood concentration of VEGF at day 3 post-injection, while MSCs tended to increase SDF-1a blood levels at 3 and 7 days post-injection. MSC-EXO enhanced the migration of irradiated endothelial cells in vitro, as compared to PBS. This effect was abrogated by TGF-ß and PI3K inhibitors. Flow cytometry analysis revealed a significant decrease in monocyte population in spleen and blood by day 3 post-injection in MSC-EXO and MSC groups compared to PBS, suggesting a larger recruitment of monocytes to the injured site in these groups. Summary/Conclusion: These results suggest that MSC-EXO exert a beneficial effect on the wound healing process in irradiation condition. In particular, MSC-EXO contributes to restore irradiated skin perfusion to normal levels. Further analyses are ongoing in order to determine MSC-EXO mechanisms of action.
ISSN:2001-3078