Cell Immunomodulatory Properties Research Articles

Correction to: Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines by Quaranta P, et al. Stem Cells Dev 2016;25(18):1321-1341 DOI:10.1089/scd.2016.0145.

Stem Cells and DevelopmentVol. 29, No. 20 CorrectionOpen AccessCorrection to: Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines by Quaranta P, et al. Stem Cells Dev 2016;25(18):1321-1341 DOI:10.1089/scd.2016.0145Published Online:7 Oct 2020https://doi.org/10.1089/scd.2016.0145.correxAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail THE AUTHORS OF THIS ARTICLE entitled Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines, published in Stem Cells Dev 2016;25;18:1321-1341 wish to correct an error.In the original Comprehensive Review, page 1321, right column, the text read as follows: Currently, naive hMSCs are employed in a large number of clinical trials successfully and, as a result, the first cell-based therapy based on allogeneic MSC-derived drugs has been approved by the Food and Drug Administration (FDA) [7].It has been revised to read as: Currently, naïve hMSCs are successfully employed in a large number of clinical trials [7] and, as a result, the first cell-based therapy based on allogenic MSCs-derived drug has been approved by theHealth Canada.In the original Comprehensive Review, page 1326, left column, the text read as follows: As a result, the drug Prochymal (Osiris Therapeutics, Inc., Columbia, MD), based on allogeneic MSCs derived from the BM of adult donors, was approved by the FDA to treat acute GVHD.It has been revised to read as: As a result, the drug ProchymalTM (Osiris Therapeutics Inc., Columbia, MD), based on allogenic MSCs derived from the BM of adult donors, was approved by theHealth Canada to treat acute GVHD.The online version of this article has been revised to reflect this correction.The authors sincerely regret this error.FiguresReferencesRelatedDetails Volume 29Issue 20Oct 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Correction to: Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines by Quaranta P, et al. Stem Cells Dev 2016;25(18):1321-1341 DOI:10.1089/scd.2016.0145.Stem Cells and Development.Oct 2020.1363-1363.http://doi.org/10.1089/scd.2016.0145.correxcreative commons licensePublished in Volume: 29 Issue 20: October 7, 2020PDF download

Improvement of Mesenchymal Stem Cell Immunomodulatory Properties by Heat-Killed Propionibacterium acnes via TLR2.

Mesenchymal stem cells (MSCs) are an essential tool for regenerative medicine, which aims to develop new technologies to improve their effects to obtain useful transplantation results. MSC immunomodulatory role has been just demonstrated; however, how they react when they are stimulated by an adjuvant is poorly understood. Our group showed the adjuvant effect of killed Propionibacterium acnes (P. acnes) on hematopoietic stem cells. As these cells share the same MSCs bone marrow (BM) site and interact with each other, here we evaluated the P. acnes and its soluble polysaccharide (PS) effect on MSCs and their immunomodulatory role in a murine model of traumatic brain injury (TBI). The bacteria increased the absolute number of MSCs, including MSC subpopulations, and maintained MSC plasticity. P. acnes and PS enhanced MSC proliferation and improved their immunomodulatory effect. P. acnes-MSC and PS-MSC transplantation increased anti-inflammatory cytokine expression and diminished pro-inflammatory cytokine expression after injury. This effect seemed to be mediated via TLR2 since P. acnes-KOTLR2-MSC transplantation decreased TGF-β and IL-10 expression. Increasing in neural stem cells and neuroblasts after PS-MSC transplantation was also observed. The adjuvant effect of P. acnes is an alternative means of expanding MSCs and important to identify their subpopulations to know better their role under exogenous stimuli including inflammation resolution in an experimental model.

Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines.

Mesenchymal Stem Cells (MSCs) can be found in various body sites. Their main role is to differentiate into cartilage, bone, muscle, and fat cells to allow tissue maintenance and repair. During inflammation, MSCs exhibit important immunomodulatory properties that are not constitutive, but require activation, upon which they may exert immunosuppressive functions. MSCs are defined as "sensors of inflammation" since they modulate their ability of interfering with the immune system both in vitro and in vivo upon interaction with different factors. MSCs may influence immune responses through different mechanisms, such as direct cell-to-cell contact, release of soluble factors, and through the induction of anergy and apoptosis. Human MSCs are defined as plastic-adherent cells expressing specific surface molecules. Lack of MHC class II antigens makes them appealing as allogeneic tools for the therapy of both autoimmune diseases and cancer. MSC therapeutic potential could be highly enhanced by the expression of exogenous cytokines provided by transduction with viral vectors. In this review, we attempt to summarize the results of a great number of in vitro and in vivo studies aimed at improving the ability of MSCs as immunomodulators in the therapy of autoimmune, degenerative diseases and cancer. We will also compare results obtained with different vectors to deliver heterologous genes to these cells.

Human Wharton's jelly–derived mesenchymal stromal cells engineered to secrete Epstein-Barr virus interleukin-10 show enhanced immunosuppressive properties

Background aimsMesenchymal stromal cells (MSCs) modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases. We hypothesized that this feature could be potentiated by co-administering anti-inflammatory cytokines. In this article, we asked whether engineering of Wharton Jelly–derived human MSCs (WJ-hMSCs) to express an anti-inflammatory cytokine increases cell immunomodulatory properties without altering their native features. MethodsWe used Epstein-Barr virus–derived interleukin-10 (vIL-10), which shares some immunosuppressive properties with human IL-10 but lacks immunostimulatory activity. Engineering was accomplished by transducing WJ-hMSCs with a self-inactivating feline immunodeficiency virus–derived vector co-expressing vIL-10 and herpes simplex virus type-1 thymidine kinase (TK). TK was added to allow future tracking of WJ-hMSC in vivo by positron electron tomography (PET). ResultsThe results show that (i) expression of TK and/or vIL-10 does not change WJ-hMSC phenotypic and functional properties; (ii) vIL-10 is secreted, biologically active and enhances the immunosuppressing functions of WJ-hMSCs; (iii) v-IL10 and TK can be produced simultaneously by the same cells and do not interfere with each other. DiscussionWJ-hMSCs engineered to secrete vIL-10 could be a powerful tool for adoptive cell therapy of immune-mediated diseases, and therefore, additional studies are warranted to confirm their efficacy in suitable animal disease models.

Unraveling the Mesenchymal Stromal Cells' Paracrine Immunomodulatory Effects.

In the last 10 years, the role of mesenchymal stromal cells (MSCs) in modulating inflammatory and immune responses has been characterized using both in vitro studies and in vivo models of immune disorders. Mesenchymal stromal cell immunomodulatory properties have been linked to various paracrine factors which expression varies depending on the pathologic condition to which the MSCs are exposed. These factors may directly impact key cells of the adaptive immune system, such as T cells. Indeed, coculturing MSCs with T cells in a mixed lymphocyte reaction assay inhibits T-cell proliferation through the secretion of immunomodulatory cytokines. However, in a context of inflammation, MSCs may secrete paracrine factors that influence other immune cell subpopulations such as dendritic cells and macrophages and polarize them toward a tolerogenic phenotype. In vivo, these same immunomodulatory factors are shown to be increased in the serum of animal models presenting with inflammatory diseases treated with MSC administration. In light of the results from these landmark studies, we review the main MSC secreted factors identified to play a role in modulating inflammatory immune responses either in vitro or in vivo, and we assess the impact of these factors on the therapeutic applications of MSC-based cell therapies in immune diseases.

Anti-CD20 Chimeric Antigen Receptor (CAR) Modified Expanded Natural Killer (NK) Cells Significantly Mediate Rituximab Sensitive and Resistant Burkitt Lymphoma (BL) Regression and Improve Survival in Human BL Xenografted NSG Mice

Epithelialemesenchymal transition (EMT) plays a central role in cancer progression and metastatic dissemination, and may be induced by local inflammation. Cell lines of lung adenocarcinoma (a549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induced by either inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) or transforming growth factor-beta. The onset of EMT triggered multiple immunosuppressive mechanisms in cancer cells resulting in NK and T cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase (IDO) pathway was the main responsible for these effects, as shown by the use of specific inhibitors. Thus, EMT induced by inflammatory stimuli confers to cancer cells immunomodulatory properties resembling those shown in mesenchymal stromal cells, which could be a cue for cancer progression and metastatic dissemination.

Correction of Post-Transplant Hematopoiesis by Novel Use of Mesenchymal-Like Placental Expanded Cells (PLX) Administered Intra-Muscular

AbstractAbstract 4133Post autologous or allogeneic stem cell transplantation hematopoietic dysfunction is a common phenomenon caused by multiple factors. Complicating the treatment of this condition is the fact that additional reserves of stem cells for autologous transplantation is usually unavailable and the use of allogeneic stem cells, if available, may be associated with transplant related complications, including graft versus host disease. Furthermore, the addition of donor cells may be ineffective because the underlying disease may also damage the supplemented stem cells. Prolonged pancytopenia in cases not responding to hematopoietic growth factors is a major life threatening condition.Bone marrow derived mesenchymal stem cells (MSC) are multi-potent cell that are being clinically explored as immune modulators and inducers of stem cell plasticity. Placental-expanded (PLX) cells are mesenchymal-like adherent stromal cells derived from the full term placenta. The cells are expanded in a bioreactor system, which provides a three dimensional microenvironment for cell growth. This system enables full control over the manufacturing process, large-scale growth of these cells and batch-to-batch consistency. PLX cells are immune privileged and suitable for allogeneic administration without HLA-Matching. Additionally, PLX cells are known to secrete a wide range of anti-inflammatory cytokines as well as various growth factors.Three patients suffered from severe and long-standing pancytopenia with associated complications after receiving hematopoietic stem cell transplantations (two allogeneic and one autologous). They were treated on a compassionated basis with intra-muscular (IM) injections of PLX cells in an attempt to enhance hematopoiesis. The first case was a 7 year-old girl that suffered from severe aplastic anemia and underwent two un-manipulated allogeneic stem cell transplantations from two different unrelated donors. The second patient was a 55 year-old woman that suffered from non-Hodgkin lymphoma and sustained an autologous stem cell transplantation. The third patient was a 45 year-old male with AML that underwent an allogeneic, un-manipulated transplant from an unrelated source.On days 74, 46, 144 post-transplant respectively for each patient, PLX cells were injected IM at a dose of 600×106 cells per adult and 160×106cell per child, divided in two administrations one week apart. No local or systemic side effects were observed. All three patients had impressive clinical improvement, which enabled them to be discharged from the hospital. The first 2 patients responded 4 and 9 days respectively after the second PLX cell administration, with improvement of tri-linage hematopoiesis. The third patient became significantly less transfusion dependent.PLX cell's immunomodulatory properties and cytokine secretory potential might be involved in the bone marrow regeneration capacity seen in these patients. The endocrine mode of action following the IM administration of PLX cells is a new and simple concept for cell therapy. Future clinical trials are needed to investigate the potential of PLX cells to enhance and shorten bone marrow engraftment following autologous or allogeneic bone marrow transplantation. Disclosures:Shoshani:Pluristem Therapeutics Inc., Haifa, Israel: Employment. Bracha:Pluristem Therapeutics Inc., Haifa, Israel: Employment. Beilin:Pluristem Therapeutics Inc., Haifa, Israel: Employment. Lior:Pluristem Therapeutics Inc., Haifa, Israel: Employment.