Studying Sjögren's syndrome in mice: What is the best available model?

Sjögren's syndrome (SS) is a common autoimmune disease characterized by lymphocytic infiltration and destruction of exocrine glands. The disease manifests primarily in the salivary and lacrimal glands, but other organs are also involved, leading to dry mouth, dry eyes, and other extra-glandular manifestations. Studying the disease in humans is entailed with many limitations and restrictions; therefore, the need for a proper mouse model is mandatory. SS mouse models are categorized, depending on the disease emergence into spontaneous or experimentally manipulated models. The usefulness of each mouse model varies depending on the SS features exhibited by that model; each SS model has advanced our understanding of the disease pathogenesis. In this review article, we list all the available murine models which have been used to study SS and we comment on the characteristics exhibited by each mouse model to assist scientists to select the appropriate model for their specific studies. We also recommend a murine strain that is the most relevant to the ideal SS model, based on our experience acquired during previous and current investigations.

Correction: Abughanam, G., et al. 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.

The authors wish to make the following corrections to this paper [...].

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

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-ß1, MMP2, CASP3, and IL-1ß. 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.

Comparative adsorption profiles of basal lamina proteome and gingival cells onto dental and titanium surfaces.

Titanium (Ti) dental implants are susceptible to bacterial infections and failure due to lack of proper epithelial seal. Epithelial cells establish a strong epithelial seal around natural teeth by the deposition of basal lamina (BL) proteins that adsorb on the tooth surface. This seal can even be re-established onto cementum or dentin following injury or periodontal therapy. However, it is unclear how tooth surfaces promote this cell attachment and protein adsorption. Understanding the interactions between BL proteins and epithelial cells with dentin and Ti will facilitate the development of implant surfaces that promote the formation of an epithelial seal and improve the success of periodontal therapy and wound healing on natural teeth. To study these interactions, we used a surface proteomic approach to decipher the adsorption profile of BL proteins onto Ti and dentin, and correlated these adsorption profiles with in vitro interactions of human gingival fibroblasts and epithelial cells. Results showed that dentin adsorbed higher amounts of key BL proteins, particularly laminin and nidogen-1, and promoted more favorable interactions with epithelial cells than Ti. Next, dentin specimens were deproteinized or partially demineralized to determine if its mineral or protein component was responsible for BL adsorption and cell attachment. Deproteinized (mineral-rich) and partially demineralized (protein-rich) dentin specimens revealed BL proteins (i.e. laminin and nidogen-1) and epithelial cells interact preferentially with dentinal proteins rather than dentin mineral. These findings suggest that, unlike Ti, dentin and, in particular, dentinal proteins have a selective affinity to BL proteins that enhance epithelial cell attachment. STATEMENT OF SIGNIFICANCE: It is remains unclear why natural teeth, unlike titanium dental implants, promote the formation of an epithelial seal that protects them against the external environment. This study used a surface screening approach to analyze the adsorption of proteins produced by epithelial tissues onto tooth-dentin and titanium surfaces, and correlate it with the behaviour of cells. This study shows that tooth-dentin, in particular its proteins, has a higher selective affinity to certain adhesion proteins, and subsequently allows more favourable interactions with epithelial cells than titanium. This knowledge could help in developing new approaches for re-establishing and maintaining the epithelial seal around teeth, and could pave the way for developing implants with surfaces that allow the formation of a true epithelial seal.

Biomaterial surface proteomic signature determines interaction with epithelial cells.

Cells interact with biomaterials indirectly through extracellular matrix (ECM) proteins adsorbed onto their surface. Accordingly, it could be hypothesized that the surface proteomic signature of a biomaterial might determine its interaction with cells. Here, we present a surface proteomic approach to test this hypothesis in the specific case of biomaterial-epithelial cell interactions. In particular, we determined the surface proteomic signature of different biomaterials exposed to the ECM of epithelial cells (basal lamina). We revealed that the biomaterial surface chemistry determines the surface proteomic profile, and subsequently the interaction with epithelial cells. In addition, we found that biomaterials with surface chemistries closer to that of percutaneous tissues, such as aminated PMMA and aminated PDLLA, promoted higher selective adsorption of key basal lamina proteins (laminins, nidogen-1) and subsequently improved their interactions with epithelial cells. These findings suggest that mimicking the surface chemistry of natural percutaneous tissues can improve biomaterial-epithelial integration, and thus provide a rationale for the design of improved biomaterial surfaces for skin regeneration and percutaneous medical devices. STATEMENT OF SIGNIFICANCE: Failure of most biomaterials originates from the inability to predict and control the influence of their surface properties on biological phenomena, particularly protein adsorption, and cellular behaviour, which subsequently results in unfavourable host response. Here, we introduce a surface-proteomic screening approach using a label-free mass spectrometry technique to decipher the adsorption profile of extracellular matrix (ECM) proteins on different biomaterials, and correlate it with cellular behaviour. We demonstrated that the way a biomaterial selectively interacts with specific ECM proteins of a given tissue seems to determine the interactions between the cells of that tissue and biomaterials. Accordingly, this approach can potentially revolutionize the screening methods for investigating the protein-cell-biomaterial interactions and pave the way for deeper understanding of these interactions.