Immunomodulatory properties of mesenchymal stem cells: Cytokines and factors

Mesenchymal stem cells (MSCs) are defined as undifferentiated cells that are capable of self renewal and differentiation into several cell types such as chondrocyte, adipocyte, osteocyte, myocyte, hepatocyte, and neuron-like cells. MSC can be isolated from bone marrow, umbilical cord blood, adipose tissue, placenta, periosteum, trabecular bone, synovium, skeletal muscle, and deciduous teeth. Immunomodulatory of MSCs is one of the important issues nowadays, because this aspect can be clinically applied for graft-versus-host and autoimmune diseases. In this review, we tried to discuss in detail about cytokines and factors such as members of the transforming growth factor superfamily (transforming growth factor-β), hepatic growth factors (HGF), prostaglandin E2 (PGE2), IL-10, indolamine 2,3-dioxygenase (IDO), nitric oxide (NO), heme oxygenase-1 (HO-1), and human leukocyte antigen-G (HLA-G) that are involved in immunomodulatory of MSCs. © 2011 John Wiley & Sons A/S

Inflammatory and Immune Responses during SARS-CoV-2 Infection in Vaccinated and Non-Vaccinated Pregnant Women and Their Newborns

Background. Pregnant women are more susceptible to severe disease associated with SARS-CoV-2 infection. We performed a prospective study to analyze the inflammatory and immune profile after SARS-CoV-2 infection occurring in vaccinated or non-vaccinated pregnant women and their newborns. Methods. Twenty-five pregnant women with SARS-CoV-2 infection were enrolled, and sixteen cord blood samples were obtained at delivery. Results. We observed that IL-1β, TNF-α, Eotaxin, MIB-1β, VEGF, IL-15, IL-2, IL-5, IL-9, IL-10 and IL-1ra levels were significantly higher in vaccinated than non-vaccinated mothers. Furthermore, the newborns of the vaccinated mothers produced higher levels of IL-7, IL-5 and IL-12 compared to the newborns of non-vaccinated mothers. Anti-Spike (S) IgG levels were significantly higher in all vaccinated mothers and their newborns compared to the non-vaccinated group. We found that 87.5% of vaccinated women and 66.6% of non-vaccinated women mounted an S-specific T-cell response quantified by ELISpot assay. Moreover, 75.0% of vaccinated mothers and 38.4% of non-vaccinated mothers showed S-specific CD4+ T-cell proliferative response. The T-helper subset response was restricted to CD4+ Th1 in both vaccinated and non-vaccinated women. Conclusion. A higher level of cytokines, IgG antibodies and memory T cells was noted in the vaccinated women. Furthermore, the maternal IgG antibody trans-placental transfer occurred more frequently in vaccinated mothers and may protect the newborn

Increased Expression of Musashi-1 Evidences Mesenchymal Repair in Maxillary Sinus Floor Elevation

This study aimed to analyze the expression of Musashi-1 (MSI1) in maxillary native bone and grafted bone after maxillary sinus floor elevation. To do so, fifty-seven bone biopsies from 45 participants were studied. Eighteen samples were collected from native bone while 39 were obtained 6 months after maxillary sinus grafting procedures. Musashi-1 was analyzed by immunohistochemistry and RT-PCR. MSI1 was detected in osteoblasts and osteocytes in 97.4% (38/39) of grafted areas. In native bone, MSI1 was detected in only 66.6% (12/18) of the biopsies, mainly in osteocytes. Detection of MSI1 was significantly higher in osteoprogenitor mesenchymal cells of grafted biopsies (p < 0.001) but minor in smooth muscle and endothelial cells; no expression was detected in adipocytes. The mesenchymal cells of the non-mineralized tissue of native bone showed very low nuclear expression of MSI1, in comparison to fusiform cells in grafted areas (0.28(0.13) vs. 2.10(0.14), respectively; p < 0.001). Additionally, the detection of MSI1 mRNA was significantly higher in biopsies from grafted areas than those from native bone (1.00(0.51) vs. 60.34(35.2), respectively; p = 0.029). Thus, our results regardig the significantly higher detection of Musashi-1 in grafted sites than in native bone reflects its importance in the remodeling/repair events that occur after maxillary sinus floor elevation in humans.This investigation was partially supported by Research Groups #CTS-138 and #CTS-1028 (Junta de Andalucía, Spain). MPM was supported by the Andalucía Talent Hub Program from the Andalusian Knowledge Agency (co-funded by the European Union’s Seventh Framework Program, Marie Skłodowska-Curie actions (COFUND – Grant Agreement n° 291780) and the Ministry of Economy, Innovation, Science and Employment of the Junta de Andalucía)

Immunological Aspects of Human Papilloma Virus-Related Cancers Always Says, “I Am like a Box of Complexity, You Never Know What You Are Gonna Get”

The human papillomavirus (HPV) can cause different cancers in both men and women. The virus interferes with functions of the cervix, vulva, vagina, anus in the anogenital area, breast, and head and neck cancer due to the local lesions. The tumors lead to death if not treated as a result of distant metastasis to internal organs and brain. Moreover, HPV attenuates the immune system during chronic infection and releases viral antigens into the tumor microenvironment. The tumors know how difficult is to win the battle with a strong united army of immune cells that are equipped with cytokines and enzymes. They confuse the immune cells with secreting viral antigens. The immune system is equipped with cytokines, a complement system, antibodies, and other secretory proteins to overcome the foreign invaders and viral antigens. However, the majority of the time, tumors win the battle without having all the equipment of the immune cells. Thus, in this review, we describe the recent progression in cellular and humoral immunity studies during the progression of HPV-related cancers. First of all, we describe the role of B, plasmoid cells, and B regulatory cells (Breg) in their functions in the tumor microenvironment. Then, different subtypes of T cells such as T CD8, CD4, T regulatory (Treg) cells were studied in recently published papers. Furthermore, NK cells and their role in tumor progression and prevention were studied. Finally, we indicate the breakthroughs in immunotherapy techniques for HPV-related cancers

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use

The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis

<p>Abstract</p> <p>Background</p> <p>ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis.</p> <p>Methods</p> <p>UCX® cells were isolated using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand <it>in vitro</it> and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR) assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed <it>in vitro.</it> Furthermore, UCX® cells were administered <it>in vivo</it> in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time.</p> <p>Results</p> <p>UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs). Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant induced arthritis model, animals treated with intra-articular (i.a.) and intra-peritoneal (i.p.) infusions of UCX® cells showed faster remission of local and systemic arthritic manifestations.</p> <p>Conclusion</p> <p>The results suggest that UCX® cells may be an effective and promising new approach for treating both local and systemic manifestations of inflammatory arthritis.</p