Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren's Syndrome.
Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren's Syndrome.
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DOI：
10.1155/2017/3134543
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发表时间：
2017
影响因子：
4.3
通讯作者：
Zoukhri D
中科院分区：
文献类型：
--
作者：
Aluri HS;Samizadeh M;Edman MC;Hawley DR;Armaos HL;Janga SR;Meng Z;Sendra VG;Hamrah P;Kublin CL;Hamm-Alvarez SF;Zoukhri D
本研究的目的是测试小鼠骨髓间充质干细胞（BD-MSCs）在干燥综合征干眼小鼠模型中改善泪液分泌的潜力，并研究相关的潜在机制。NOD小鼠（n = 20）随机接受无菌磷酸盐缓冲盐水（PBS，对照）或鼠BD-MSC（1 × 106个细胞）腹腔注射。在基线和治疗后每周一次使用酚红浸渍线测量泪液产生。在治疗结束时测量泪液中的组织蛋白酶S活性。4周后，处死动物，切除泪腺并进行组织病理学、免疫组织化学和RNA分析。在BD-MSC注射后，与基线和PBS注射的小鼠相比，眼泪产生随时间增加。尽管治疗动物泪腺中淋巴细胞灶的数量没有变化，但与对照动物相比，灶的大小减少了40.5%。水通道水通道蛋白5的mRNA水平显着增加后交付的BD-MSC。我们得出结论，BD-MSCs治疗增加了干燥综合征NOD小鼠模型的泪液产生。这可能是由于炎症减少和水通道蛋白5的表达增加。
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.