scholarly journals The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Ana G. Serrato López ◽  
Juan J. Montesinos Montesinos ◽  
Santiago R. Anzaldúa Arce
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Veterinary Medicine ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Domestic Animals ◽  
Clinical Tool ◽  
Cellular Contact ◽  
Activated T Lymphocytes

Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.Figure 1: Immunoregulatory ability of MSCs. MSCs regulate the functions of NK cells, dendritic cells (DC) and T lymphocytes. The immunosuppressive effect may occur through the secretion of different factors or through cellular contact (black arrows). The former pathway involves TGFß, HGF, IL-10, PGE2, and HLA-G5, whereas the latter pathway involves the products of IDO enzyme activity, PD-L1, HLA-G1, ICAM-I and VCAM-I. Pro-inflammatory cytokines (IFN-?) secreted by NK cells and activated T lymphocytes favour the immunoregulatory activity of MSCs (dotted lines), because they increase or induce the secretion of molecules that regulate the functions of the distinct cellular components of the immune system. Modified from Montesinos et al, and Ma et al.19,66

scholarly journals The Effects of Mesenchymal Stem Cells on Antimelanoma Immunity Depend on the Timing of Their Administration

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Dragana Miloradovic ◽  
Dragica Miloradovic ◽  
Bojana Simovic Markovic ◽  
Aleksandar Acovic ◽  
Carl Randall Harrell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Tumor Growth ◽  
Nk Cells ◽  
Plasma Levels ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Granzyme B ◽  
Lower Plasma

There is still a lively debate about whether mesenchymal stem cells (MSCs) promote or suppress antitumor immune response. Although several possible explanations have been proposed, including different numbers of injected and engrafted MSCs, heterogeneity in phenotype, and function of tumor cells, the exact molecular mechanisms responsible for opposite effects of MSCs in modulation of antitumor immunity are still unknown. Herewith, we used a B16F10 murine melanoma model to investigate whether timing of MSC administration in tumor-bearing mice was crucially important for their effects on antitumor immunity. MSCs, intravenously injected 24 h after melanoma induction (B16F10+MSC1d-treated mice), significantly enhanced natural killer (NK) and T cell-driven antitumor immunity, suppressed tumor growth, and improved survival of melanoma-bearing animals. Significantly higher plasma levels of antitumorigenic cytokines (TNF-α and IFN-γ), remarkably lower plasma levels of immunosuppressive cytokines (TGF-β and IL-10), and a significantly higher number of tumor-infiltrating, IFN-γ-producing, FasL- and granzyme B-expressing NK cells, IL-17-producing CD4+Th17 cells, IFN-γ- and TNF-α-producing CD4+Th1 cells, and CD8+cytotoxic T lymphocytes (CTLs) were observed in B16F10+MSC1d-treated mice. On the contrary, MSCs, injected 14 days after melanoma induction (B16F10+MSC14d-treated mice), promoted tumor growth by suppressing antigen-presenting properties of tumor-infiltrating dendritic cells (DCs) and macrophages and by reducing tumoricidal capacity of NK cells and T lymphocytes. Significantly higher plasma levels of TGF-β and IL-10, remarkably lower plasma levels of TNF-α and IFN-γ, and significantly reduced number of tumor-infiltrating, I-A-expressing, and IL-12-producing macrophages, CD80- and I-A-expressing DCs, granzyme B-expressing CTLs and NK cells, IFN-γ- and IL-17-producing CTLs, CD4+Th1, and Th17 cells were observed in B16F10+MSC14d-treated animals. In summing up, the timing of MSC administration into the tumor microenvironment was crucially important for MSC-dependent modulation of antimelanoma immunity. MSCs transplanted during the initial phase of melanoma growth exerted tumor-suppressive effect, while MSCs injected during the progressive stage of melanoma development suppressed antitumor immunity and enhanced tumor expansion.

Evidence for Killing of Mesenchymal Stem Cells (MSC) by Autologous Natural Killer Lymphocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1290-1290 ◽  
Author(s):  
Alessandro Poggi ◽  
Anna-Maria Massaro ◽  
Simone Negrini ◽  
Ivana Pierri ◽  
Manuela Balocco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Viral Infections ◽  
Nk Cell ◽  
Cell Lineage ◽  
Culture Conditions ◽  
Inhibitory Receptors

Abstract In this study, Mesenchymal Stem Cells (MSC) were obtained from bone marrow of 10 patients suffering from acute myeloid leukemia (AML), six M0/1 two M2, and two M5 (according to the FAB classification), 8 out of 10 in post-chemotherapy complete remission. These cells differentiated into adipocytes or osteoblasts under appropriate culture conditions. MSC were CD44+, CD73a+ CD73b+ CD105+, beta1 integrin+, ICAM1+, HLA-I+, HLA-II+ (variable proportions), CD45−, CD31−, CD34− and they constitutively expressed the stress-inducible MHC-related molecules MIC-A and the UL16 (induced at the surface of cells infected by cytomegalovirus) binding protein ULBP3. These molecules are reported ligands for the NKG2D receptor expressed by natural killer (NK) and CD8+ T lymphocytes, effector cells that are thought to play a role in host defence against tumors. NK cells have also been shown to regulate normal differentiation of hemopoietic precursor into the myeloid or lymphoid cell lineage. Moreover, it has been stated that NK cells are not able to damage autologous cells, as they receive negative signals through inhibitory receptors, including killer Ig-like receptors (KIR) or C-type lectin inhibitory receptors (CLIR), which bind to HLA-I discrete alleles. Surprisingly, we found that autologous IL2-activated, but not freshly isolated, NK cells lysed MSC, while T lymphocytes did not kill self or non-self MSC. Binding of ICAM-1 expressed by MSC to its receptor, the integrin LFA-1, expressed by NK cells plays a key role in MSC/NK interaction. More importantly, NKG2D/MICA and/or NKG2D/ULBP3 engagement is responsible for the delivery of lethal hit. Conversely, it appears that HLA-I molecules do not protect MSC from NK cell-mediated injury. Taken together, these data suggest that NK cells, when activated as it may occur during the first response to viral infections, are able to eliminate MSC, thus altering the normal interactions with hemopoietic precursors and possibly affecting their differentiation. This mechanism might also contribute to the development of aberrant precursors as observed in acute leukaemias.

scholarly journals BIOTECNOLOGIA DE CÉLULAS TRONCO MESENQUIMAIS: PRINCIPAIS APLICAÇÕES EM MEDICINA VETERINÁRIA E PERSPECTIVAS GERAIS

2017 ◽  
Vol 13 (Especial 2) ◽  
pp. 83-89
Author(s):  
Elaine Cristina Galhardo ◽  
Ariane Dantas ◽  
Aline Sousa Camargos ◽  
Fernanda da Cruz Landim
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Veterinary Medicine ◽  
In Vitro Culture ◽  
Adult Tissues ◽  
Inflammatory Processes ◽  
Specific Tissue

Mesenchymal Stem Cells (MSCs) are isolated from adult tissues and presents ability to originate identical cells or differentiate into specific tissue cells. Studies about in vitro culture and in vivo application of MSCs have pointed the potential to be explored in regenerative treatments and modulation of inflammatory processes, as well as the improvement of tissue engineering techniques and the development of biomaterials. Veterinary Medicine has presented, in several species, satisfactory results coming from the regenerative potential and paracrine activity characteristic of the MSCs. This review aimed, briefly showing promising results of the experimental MSCs application in Veterinary Medicine, its current biotechnological overview and general prospects.

scholarly journals Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro

Hematology ◽  
2017 ◽  
Vol 23 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Chen Liang ◽  
Erlie Jiang ◽  
Jianfeng Yao ◽  
Mei Wang ◽  
Shulian Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Interferon Γ ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy

2021 ◽  
pp. 2588-2595
Author(s):  
Dwi Liliek Kusindarta ◽  
Hevi Wihadmadyatami
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Veterinary Medicine ◽  
Umbilical Cord ◽  
Ethical Issues ◽  
Domestic Animals ◽  
Hematopoietic Stem ◽  
Efficient Treatment ◽  
Major Interest ◽  
Umbilical Cords

Umbilical cord blood (UCB) cells are an important source of mesenchymal stem cells (MSCs). It is known that the umbilical cord is rich in hematopoietic stem cells, which influenced research on ontogeny and transplantation (allogeneic transplantation). In recent years, stem cell research has emerged as an area of major interest due to its prospective applications in various aspects of both human and veterinary medicine. Moreover, it is known that the application of MSCs has several weaknesses. The use of these cells has limitations in terms of tumorigenesis effect, delivery, safety, and variability of therapeutic response, which led to the use of secretomes as an alternative to cell-free therapy. The main obstacle in its use is the availability of human UCB as an origin of MSCs and MSCs' secretomes, which are often difficult to obtain. Ethical issues regarding the use of stem cells based on human origin are another challenge, so an alternative is needed. Several studies have demonstrated that MSCs obtained from bovine umbilical cords have the same properties and express the same surface markers as MSCs obtained from human umbilical cords. Therefore, secretomes from MSCs derived from domestic animals (bovine) can possibly be used in human and veterinary medicine. This finding would contribute significantly to improve cell-free therapy. At present, the use of UCB MSCs derived from domestic animals, especially bovines, is very restricted, and only limited data about bovine UCB are available. Therefore, the aim of this review was to provide an updated overview of cell-free therapy and discuss the new possibilities introduced by the generation of this therapy derived from bovine umbilical MSCs as a promising tool in developing modern and efficient treatment strategies.

scholarly journals Immunomodulatory Effect of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells on Activated T-lymphocyte

2021 ◽  
Author(s):  
Parisa Lotfinejad ◽  
Karim Shamsasenjan ◽  
Behzad Baradaran ◽  
Elham Safarzadeh ◽  
Tohid Kazemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Immunomodulatory Effects ◽  
Tnf Α ◽  
Activated T Lymphocytes ◽  
Ifn Γ

Many studies have been performed about regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) and their application in different treatment approaches. The present study aimed to investigate the immunomodulatory effect of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on the gene expression profile of cytokines in stimulated T-lymphocytes. For this purpose, MSCs were isolated from umbilical cord blood samples and cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. The nature of MSCs was identified by flow cytometry analysis and differentiation to the adipocyte and osteocyte lineage. Moreover, to investigate the immunomodulatory effects of MSCs on T cells, a co-culture system was designed and expression levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β) genes were measured; using the real-time polymerase chain reaction (RT-PCR) technique. Our results demonstrated the ability of MSCs to differentiate into adipocyte and osteocyte lineages. Further investigation also displayed that although UCB-MSCs could significantly reduce the expression of pro-inflammatory cytokines like IL-2, IL-6, IFN-γ, and TNF-α in activated T-lymphocytes, they noticeably potentiated the expression levels of IL-4, IL-10, IL-13, and TGF-β in the co-culture setting. In conclusion, UCB-MSCs have immunomodulatory effects on activated T-lymphocytes in favor of anti-inflammatory responses.

scholarly journals Mesenchymal stem cells promote the sustained expression of CD69 on activated T lymphocytes: roles of canonical and non-canonical NF-κB signalling

2012 ◽  
Vol 16 (6) ◽  
pp. 1232-1244 ◽  
Author(s):  
Felipe Saldanha-Araujo ◽  
Rodrigo Haddad ◽  
Kelen C. R. Malmegrim de Farias ◽  
Alessandra de Paula Alves Souza ◽  
Patrícia V. Palma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Activated T Lymphocytes

scholarly journals Mesenchymal Stem Cells Promote Metastasis of Lung Cancer Cells by Downregulating Systemic Antitumor Immune Response

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Marina Gazdic ◽  
Bojana Simovic Markovic ◽  
Nemanja Jovicic ◽  
Maja Misirkic-Marjanovic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Cancer ◽  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Cancer Metastasis ◽  
Antitumor Immune Response ◽  
Lung Cancer Metastasis

Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice. MSCs profoundly reduced infiltration of macrophages, TNF-α-producing dendritic cells (DCs), TNF-α-, and IL-17-producing CD4+ T cells but increased IL-10-producing CD4+ T lymphocytes in the lungs of tumor-bearing animals. The total number of lung-infiltrated, cytotoxic FasL, perforin-expressing, TNF-α-, and IL-17-producing CD8+ T lymphocytes, and NKG2D-expressing natural killer (NK) cells was significantly reduced in LLC1 + MSC-treated mice. Cytotoxicity of NK cells was suppressed by MSC-conditioned medium. This phenomenon was abrogated by the inhibitors of inducible nitric oxide synthase (iNOS) and indoleamine 2,3-dioxygenase (IDO), suggesting the importance of iNOS and IDO for MSC-mediated suppression of antitumor cytotoxicity of NK cells. This study provides the evidence that MSCs promote lung cancer metastasis by suppressing antitumor immune response raising concerns regarding safety of MSC-based therapy in patients who have genetic susceptibility for malignant diseases.

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