Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Saleh, Soad; Parhar, Ranjit S.; Al-Hejailan, Reem S; Bakheet, Razan; Khaleel, Hala S; Khalak, Hanif; Halees, Anason S.; Zaidi, Marya Z.; Meyer, Brian F.; Yung, Gisella Puga; Conca, Walter; Khabar, Khalid S.A.; Collison, Kate S.; Al‐Mohanna, Futwan

doi:10.4049/jimmunol.1300601

Cited by 11 publications

(8 citation statements)

References 65 publications

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“…CD59 and CD99 and play a role in of T-cells activation and migration (Kimberley et al, 2007), whereas CD68 promotes macrophage activation (Ji, 2012). CD40, CD46, CD81, and CD82 are immune-costimulatory antigens which promote the activation of different cells of the immune system (Levy et al, 1998; Shibagaki et al, 1998; Zaffran et al, 2001; Elgueta et al, 2009; Johnson and Ruffell, 2009; Saleh et al, 2013). In parallel, CBD treatment led to the upregulation of antigens which negatively regulate T cell activation via the disruption of APC/T interactions as well as of antigen processing and presentation, such as CD47, CD55, and CD276.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

et al. 2016

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Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5 μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis. In particular, we have demonstrated that CBD treatment in hGMSCs prevented the activation of the NALP3-inflammasome pathway by suppressing the levels of NALP3, CASP1, and IL18, and in parallel, inhibited apoptosis, as demonstrated by the suppression of Bax. CBD treatment was also able to modulate the expression of the well-known mesenchymal stem cell markers (CD13, CD29, CD73, CD44, CD90, and CD166), and other surface antigens. Specifically, CBD led to the downregulation of genes codifying for antigens involved in the activation of the immune system (CD109, CD151, CD40, CD46, CD59, CD68, CD81, CD82, CD99), while it led to the upregulation of those implicated in the inhibition of the immune responses (CD47, CD55, CD276). In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

et al. 2016

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“…Other intercellular signaling components, such as the tetraspanins CD82 and CD63, were also most differentially expressed. CD82 function has recently been linked to the recognition and rejection of xenogeneic porcine aortic endothelial cells by human monocytes and neutrophils (Saleh et al, 2013). Mast cells expressed high amounts of CD82 (Table S2), and thus might exert similar functions in recognition and rejection of xenogeneic cells.…”

Section: Human Mast Cell Proteome Contains Receptors For Multifaceted Interactions With Tissue Environmentsmentioning

confidence: 99%

Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation

et al. 2020

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Mast cells are rare tissue-resident cells of importance to human allergies. To understand the structural basis of principle mast cell functions, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast-cell-specific proteome signature, indicative of a unique lineage, only distantly related to other immune cell types, including innate immune cells. Proteome comparison between human and mouse suggested evolutionary conservation of core mast cell functions. In addition to specific proteases and proteins associated with degranulation and proteoglycan biosynthesis, mast cells expressed proteins potentially involved in interactions with neurons and neurotransmitter metabolism, including cell adhesion molecules, ion channels, and G protein coupled receptors. Toward targeted cell ablation in severe allergic diseases, we used MRGPRX2 for mast cell depletion in human skin biopsies. These proteome analyses suggest a unique role of mast cells in the immune system, probably intertwined with the nervous system.

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“…Human neutrophils were isolated from peripheral blood of healthy donors essentially as described previously. 20…”

Section: Preparation Of Human Naive Neutrophilsmentioning

confidence: 99%

Toward allogenizing a xenograft: Xenogeneic cardiac scaffolds recellularized with human‐induced pluripotent stem cells do not activate human naïve neutrophils

et al. 2021

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The limited availability of human donor organs suitable for transplantation has resulted in ever-increasing patient waiting lists globally. Xenotransplantation is considered a potential option, but is yet to reach clinical practice. Although remarkable progress has been made in overcoming immunological rejection, issues with functionality are still to be resolved. Bioengineering approaches have been used to create cardiac tissues with optimized functions. The use of decellularized xenogeneic cardiac tissues seeded with donor-derived cardiac cells may prove to be a viable strategy as supporting structures of the native tissue such as vasculature can be utilized. Here we used sequential perfusion to decellularize adult rat hearts. The acellular scaffolds were reseeded with human endothelial cells, human fibroblasts, human mesenchymal stem cells, and cardiac cells derived from human-induced pluripotent stem cells. The ability of the resultant recellularized rat scaffolds to activate human naïve neutrophils in vitro was investigated to measure xenogeneic recognition. Our results demonstrate that in contrast to cadaveric xenogeneic hearts, acellular and recellularized xenogeneic scaffolds did not activate human naïve neutrophils and suggest that decellularization removes the xenogeneic antigens that lead to human naïve neutrophil activation thus allowing human cells to populate the now "allogenized" xenogeneic scaffolds.

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Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Cited by 11 publications

References 65 publications

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation

Toward allogenizing a xenograft: Xenogeneic cardiac scaffolds recellularized with human‐induced pluripotent stem cells do not activate human naïve neutrophils

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