Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren’s Syndrome

Abstract

The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren's syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n = 20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 106 cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads. Cathepsin S activity in the tears was measured at the end of treatment. After 4 weeks, animals were sacrificed and the lacrimal glands were excised and processed for histopathology, immunohistochemistry, and RNA analysis. Following BD-MSC injection, tears production increased over time when compared to both baseline and PBS injected mice. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% when compared to control animals. The mRNA level of the water channel aquaporin 5 was significantly increased following delivery of BD-MSCs. We conclude that treatment with BD-MSCs increases tear production in the NOD mouse model of Sjögren's syndrome. This is likely due to decreased inflammation and increased expression of aquaporin 5.

Establishment of long-term serum-free culture for lacrimal gland stem cells aiming at lacrimal gland repair

“…Previous studies have reported that mesenchymal stem cell (MSC) therapy is an alternative strategy for treatment of DED, which could suppress inflammation and ROSA-LGSCs cultured for 7 or 14 days were used for the treatment of aqueousdeficient dry eye disease (ADDED) mice. The success ratio of engraftment of ROSA-LGSCs cultured for 7 days was much higher than ROSA-LGSCs cultured for 14 days increase tear production [45,46]. As several reports have described MSCs transplanted by vein injection [47,48], we first attempted to transplant the LGSCs into NOD/ ShiLtJ mice by tail vein injection.…”

Mesenchymal Stem Cells in Primary Sjögren’s Syndrome: Prospective and Challenges

“…Another team finds that treatment with BMSCs prevents a decline in the salivary flow rate and lymphocytic infiltrations in the salivary glands of NOD mice [ 94 ]. Furthermore, BMSCs enhance tear production in the NOD mouse model, due to decreased inflammation and increased expression of aquaporin 5 [ 95 ]. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% [ 95 ].…”

“…Furthermore, BMSCs enhance tear production in the NOD mouse model, due to decreased inflammation and increased expression of aquaporin 5 [ 95 ]. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% [ 95 ].…”

Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy

“…The immunomodulatory capacity of MSCs is also complemented by their important potential to promote the generation and maintenance of the activity of different types of regulatory T cells [ 54 , 67 , 75 ]. Regulatory T cells are cell mediators of peripheral immunological tolerance, and their absence results in excessive multisystem autoimmunity [ 77 , 78 ].…”

“…MSCs implantation by different routes has raised very interesting expectations in the treatment of dry eye and regeneration of the ocular surface, thanks to their capacities of immunomodulation and regenerative potential [ 78 , 79 ]. MSC therapy in experimental DES syndrome models improved tear volume and tear film stability, increasing epithelial recovery and the number of goblet cells and decreasing the number of meibomian gland injuries in the conjunctiva [ 77 , 80 ]. Decreasing CD4+ T cells and proinflammatory factors (IL-2, interferon-gamma (IFN-γ), IL-17, and MMP-2) and increasing anti-inflammatory T cell responses augments the regulatory T cells, preventing the progression of the process [ 80 ].…”