Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis

Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-γ. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases. Copyright © 2009 by The American Association of Immunologists, Inc

Immunological characterization of multipotent mesenchymal stromal cells--The International Society for Cellular Therapy (ISCT) working proposal.

Disclosure of interests: The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.International audienceCultured mesenchymal stromal cells (MSCs) possess immune regulatory properties and are already used for clinical purposes, although preclinical data (both in vitro and in vivo in animal models) are not always homogeneous and unequivocal. However, the various MSC-based clinical approaches to treat immunological diseases would be significantly validated and strengthened by using standardized immune assays aimed at obtaining shared, reproducible and consistent data. Thus, the MSC Committee of the International Society for Cellular Therapy has decided to put forward for general discussion a working proposal for a standardized approach based on a critical view of literature data

Do mutations turn p53 into an oncogene?

The key role of p53 as a tumor suppressor became clear when it was realized that this gene is mutated in 50% of human sporadic cancers and germline mutations expose to cancer along lifespan. Mutations in this gene not only abolish the tumor suppressive functions of p53 but also equip the protein with new pro-oncogenic functions. Here, we review the mechanisms by which these new functions gained by p53 mutants promote tumorigenesis

The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth

Mesenchymal stem cells (MSCs) have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance

Immunomodulatory properties of stem cells from human exfoliated deciduous teeth

Extent: 10p.Introduction: Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs). Methods: We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice. Results: We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGFβ, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells. Conclusions: These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.Takayoshi Yamaza, Akiyama Kentaro, Chider Chen, Yi Liu, Yufang Shi, Stan Gronthos, Songlin Wang, Songtao Sh

CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation

Antigen-induced immune suppression, like T cell activation, requires antigen-presenting cells (APCs); however, the role of APCs in mediating these opposing effects is not well understood, especially in vivo. We report that genetic inactivation of CD11b, which is a CD18 subfamily of integrin receptors that is highly expressed on APCs, abolishes orally induced peripheral immune tolerance (oral tolerance) without compromising APC maturation or antigen-specific immune activation. The defective oral tolerance in CD11b−/− mice can be restored by adoptive transfer of wild-type APCs. CD11b deficiency leads to enhanced interleukin (IL) 6 production by APCs, which subsequently promotes preferential differentiation of naive T cells to T helper 17 (Th17) cells, which are a T cell lineage characterized by their production of IL-17. Consequently, antigen feeding and immunization of CD11b−/− mice results in significant production of IL-17 within the draining lymph nodes that interferes with the establishment of oral tolerance. Together, we conclude that CD11b facilitates oral tolerance by suppressing Th17 immune differentiation

Is hydroxychloroquine beneficial for COVID-19 patients?

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world1-3, the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 20204. The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir5, to control the disease and halt the pandemic

Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases

Unlike T cells restricted by major histocompatibility complex (MHC) class Ia or class II molecules, T cells restricted by MHC class I–like molecules demonstrate properties of both innate and adaptive immunity and are therefore considered innate-like lymphocytes (ILLs). ILLs are believed to have immunoregulatory functions, but their roles in autoimmunity and defense against infections remain elusive. To study the properties of ILLs, we generated mice expressing only MHC class I–like molecules by crossing CIITA−/− with Kb−/−Db−/− mice. Surprisingly, these mice developed a lymphoproliferative syndrome and autoimmunity, most notably inflammatory bowel disease (IBD) and insulitis. The CD8+ ILLs in these mice exhibit a constitutively activated phenotype, and depletion of these cells abolished the autoimmune disorders. In addition, adoptive transfer of CD8+ ILLs from Kb−/−Db−/−CIITA−/− mice to Rag-1−/−pfn−/− mice also resulted in IBD and insulitis. These findings provide direct evidence that CD8+ ILLs are sufficient to initiate and mediate autoimmune diseases