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Mahta Samizadeh, Hema Aluri, Helene L Armaos, Claire Kublin, Driss Zoukhri; Delivery of bone marrow-derived mesenchymal stem cells improves tear production in a mouse model of Sjögren’s Syndrome. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3462.
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© ARVO (1962-2015); The Authors (2016-present)
Several studies documented the modulatory and healing properties of bone marrow- derived mesenchymal stem cells (BD-MSCs) in numerous diseases. The purpose of the present studies was to test the potential of BD-MSCs to restore normal tear production in a mouse model of Sjögren’s syndrome.
BD-MSCs isolated from C57BL/6-Tg(UBC-GFP) mice were a generous gift from Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White. NOD mice (n=6) were randomized to either receive i.p. injections of PBS (control) or BD-MSCs (1x106 in 0.2 ml of PBS, 0.1 ml injected on each side).Tear production was measured at baseline and once a week for 3 weeks, using phenol red impregnated threads and expressed in mm/10s. After 3 weeks, animals were sacrificed and the lacrimal glands excised and processed for histopathology to determine the number and the size of lymphocytic foci. Samples were also processed for immunohistochemistry using antibodies against Foxp3, a transcription factor known to be expressed by T regulatory cells. The number of Foxp3 positive cells in each lymphocytic focus was quantified, on serial sections, using ImageJ software and expressed as a percent of total (DAPI stained) number cells in the focus.
Following BD-MSCs injection, tear production increased overtime to a maximum 2.4-fold increase over baseline values (6.8 ± 1.5 vs. 2.8 ± 1.1, p<0.05, n=3). In contrast, tear production did not increase in PBS injected animals (2.4 ± 0.5 vs. 3.2 ± 0.9, p>0.05, n=3). The number of lymphocytic foci did not differ between the 2 groups (BD-MSCs: 2.93 ± 0.24, PBS: 2.92 ± 0.19, p>0.05, n=3). In contrast, there was a ~37% decrease in the size of the lymphocytic infiltrates in BD-MSCs treated lacrimal glands (BD-MSCs: 7.1 ± 0.9, PBS: 11.5 ± 1.5, p<0.05, n=3). Similarly, the number of Foxp3+ cells increased by ~28% in BD-MSCs treated lacrimal glands.
We conclude that a single i.p. injection of BD-MSCs increased tear production in a mouse model of Sjögren’s syndrome. Our data also suggest that the immuno-modulatory effect of BD-MSCs might involve a shift in the cellular composition of the lymphocytic infiltrates within the lacrimal gland. Further studies needed to test this hypothesis.<br />
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