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Abstract
Sjogren’s syndrome (SS) is an autoimmune disease that manifests primarily in salivary and lacrimal glands leading to dry mouth and eyes. Unfortunately, there is no cure for SS due to its complex etiopathogenesis. Mesenchymal stem cells (MSCs) were successfully tested for SS, but some risks and limitations remained for their clinical use. This study combined cell- and biologic-based therapies by utilizing the MSCs extract (MSCsE) to treat SS-like disease in NOD mice. We found that MSCsE and MSCs therapies were successful and comparable in preserving salivary and lacrimal glands function in NOD mice when compared to control group. Cells positive for AQP5, AQP4, α-SMA, CK5, and c-Kit were preserved. Gene expression of AQP5, EGF, FGF2, BMP7, LYZ1 and IL-10 were upregulated, and downregulated for TNF-α, TGF-β1, MMP2, CASP3, and IL-1β. The proliferation rate of the glands and serum levels of EGF were also higher. Cornea integrity and epithelial thickness were maintained due to tear flow rate preservation. Peripheral tolerance was re-established, as indicated by lower lymphocytic infiltration and anti-SS-A antibodies, less BAFF secretion, higher serum IL-10 levels and FoxP3+ Treg cells, and selective inhibition of B220+ B cells. These promising results opened new venues for a safer and more convenient combined biologic- and cell-based therapy.
Highlights
Sjogren’s syndrome (SS) is a common progressive autoimmune disease that affects females predominantly [1,2,3]
We have reported in previous studies that Bone marrow (BM) cells and compact bone-derived Mesenchymal stem cells (MSCs) have successfully preserved the salivary gland function when injected into female non-obese diabetic mice (NOD) mice [49,76]
We have found that in the submandibular and lacrimal glands of MSCs-/MSCs extract (MSCsE)-treated groups the apical expression of AQP5 was upregulated as measured by the immunofluorescence staining whereas in the control group, AQP5 was expressed partially at the apical surface with very low intensity, and the same applies to AQP4
Summary
Sjogren’s syndrome (SS) is a common progressive autoimmune disease that affects females predominantly [1,2,3]. SS progresses slowly and patients exhibit clinical symptoms years after the disease onset [12]. The immune system targets epithelial tissues, infiltrates it with lymphocytes, and later forms autoantibodies against glands antigens [3,13,14,15,16]. The aberrant immune dysregulation leads to the destruction of epithelial tissues, especially salivary and lacrimal glands, and to several extra-glandular manifestations. The current SS management is symptomatic-based to alleviate the dryness severity and complications [21,22]. Patients with systemic involvement and serious complications are prescribed immunosuppressant and disease-modifying antirheumatic drugs [23,24,25]. The current management is not adequate nor satisfactory, leading to a compromised quality of life [26,27,28]
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