New perspectives for the treatment of Dry Eye Disease secondary to Sjögren’s syndrome: cell therapy with injection of mesenchymal stem cells in the lacrimal glands - an experimental study

Abstract

Purpose : To evaluate the therapeutic effect of injecting mesenchymal stem cells (MSCs) derived from immature dental pulp in the lacrimal glands of an experimental model of Dry Eye Disease (DED) secondary to Sjögren’s Syndrome (SS).

Methods : MSCs were grown in a specific culture medium and submitted to the cell viability test. To perform the cell therapy, we first confirmed that the animals developed SS and DED. 2x10⁴ cells/5uL were injected in the right lacrimal gland of the female mice of the NOD/MRK strain (TR, n=11 for clinical analyses and n=5 for PCR analysis). Mice of C57BL strain were used as healthy control (CT, n=5), and NOD/MRK mice without treatment for the sick control (NOD, n=5 ). Clinical assessments were performed by measuring tear production with cotton threads (Phenol Red) and keratitis through slit-lamp biomicroscopic exam with fluorescein staining at three different times: day of cell application (baseline), and after 7 and 14 days of treatment. Mice were euthanized on the 14th day after treatment. Lacrimal glands were collected to perform qRT-PCR using IL-6 and IL-10 primers. The groups were compared using a one-way analysis of variance, and a significance value of p<0.05 was adopted.

Results : The MSCs showed a 98% cell viability rate. In the clinical analyses of the right eye, the TR group showed a statistically significant reduction of keratitis after 14 days of treatment compared to the NOD group. The tear production in the TR group significantly increased after 7 and 14 days of treatment compared to the NOD group and with the baseline time. In the left eye, a significant reduction of keratitis was also observed after 14 days of treatment when compared to the NOD group. After 7 and 14 days of treatment, the TR group showed no statistically significant difference with the CT group, suggesting a contralateral effect of the treatment on DED. In the PCR analysis of the right lacrimal glands, the TR group obtained a significant increase in IL-6 and IL-10 gene expression compared to the CT and NOD groups.

Conclusions : Cell therapy significantly increased tear production and reduced keratitis in NOD mice. When combined with increased expression of IL-6 and IL-10, data from clinical analysis corroborated the literature indicating that MSCs injected in the lacrimal glands are improving signs of DED.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.