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Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren’s Syndrome-Like Disease

McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada
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Int. J. Mol. Sci. 2019, 20(19), 4750; https://doi.org/10.3390/ijms20194750
Received: 28 August 2019 / Revised: 19 September 2019 / Accepted: 20 September 2019 / Published: 25 September 2019
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine)
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. View Full-Text
Keywords: Sjogren’s syndrome (ss); autoimmune diseases; biologic therapy; bone marrow; cell extract; lacrimal gland; mesenchymal stem cells (MSCs); non-obese diabetic mice (NOD); salivary glands; submandibular glands Sjogren’s syndrome (ss); autoimmune diseases; biologic therapy; bone marrow; cell extract; lacrimal gland; mesenchymal stem cells (MSCs); non-obese diabetic mice (NOD); salivary glands; submandibular glands
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Abughanam, G.; Elkashty, O.A.; Liu, Y.; Bakkar, M.O.; Tran, S.D. Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren’s Syndrome-Like Disease. Int. J. Mol. Sci. 2019, 20, 4750.

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