间充质干细胞外泌体治疗小鼠干眼的疗效评价

Objective To investigate the therapeutic effects of human umbilical cord mesenchymal stem cells derived exosomes (MSC-Exo) on a mouse model of dry eye. Methods Thirty-two healthy adult male BALB/c mice (64 eyes) aged 6-8 weeks were selected in this study and divided into four groups randomly (group A, B, C and D), with each group consisting of 8 mice. The dry eye model was induced by eye drop of 2 g • L"1 benzalkonium chloridefor 14 consecutive days in group A, group B and group C. Group D served as the normal controls without any treatment. The A group was given 25 g ¦ L"' MSC-Exo eye drops, while the group B was given PBS eye drops and the group C were not received any treatment as the negative control. The Schirmer I test (SIT), tear break-up time (BUT) and corneal fluorescein staining (FL) were evaluated before and after eye drops on day 1, day 4 and day 7. The cornea samples of all mice were collected for histological investigation of corneal epithelium using hematoxylin and eosin staining, and ultrastructure of corneal epithelial cells was further examined by transmission electron microscopy (TEM). Results There were no statistical changes in SIT, BUT before therapy and 1 day after treatment among group A, group B and group C, and no statistical changes in FL between group A and group B at both time points. Moreover there were significant differences in SIT, BUT between group A, B, C and group D (all P < 0. 05). Significantly more tear volume and longer BUT were shown on day 4 and day 7 after treatment in group A than group B and group C (all P < 0. 05). On day 4 and day 7 after treatment, SIT and BUT were significantly increased in group A (both P<0. 05), and FL score was lower than before treatment (P < 0. 05). There were no significant differences in SIT, BUT, FL before and after treatment in group B (all P > 0. 05). No treatment was performed after modeling in group C, and no treatment was performed in group D. There were no significant changes in parameters of the two groups (all P > 0. 05). TEM showed that the number of microvilli of corneal epithelium was large in group A, and they arranged neatly and had finger-like protrusions;the microvilli in group B decreased, shortened and arranged disorderly; they were significantly reduced, shedding, and missing, and their arrangement was disordered in group C, while the microvilli in group D were finger-like, neatly arranged and numerous. Group C was very different from group A and group D. Conclusion The exosomes derived from mesenchymal stem cells exhibit signicantly therapeutic effects on dry eye mice model, which suggest that MSC-Exo administration is a promising method for the treatment of dry eye.