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      Inhibitory Effect of Bovine Adipose-Derived Mesenchymal Stem Cells on Lipopolysaccharide Induced Inflammation of Endometrial Epithelial Cells in Dairy Cows

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          Abstract

          Endometritis is a disease that affects reproductive health in dairy cows and causes serious economic damage to the dairy industry world-wide. Although in recent years, the application of mesenchymal stem cell (MSC) therapy for the treatment of inflammatory diseases has attracted much attention, there are few reports of the use of MSCs in dairy cows. In the present study, our objective was to explore the inhibitory effects of bovine adipose-derived mesenchymal stem cells (bAD-MSCs) on lipopolysaccharide (LPS) induced inflammation in bovine endometrial epithelial cells (bEECs) along with the potential underlying molecular mechanisms. We characterized isolated bAD-MSCs using cell surface marker staining and adipogenic/osteogenic differentiation, and analyzed them using immunofluorescence, flow cytometry (surface marker staining), and adipogenic and osteogenic differentiation. Furthermore, to understand the anti-inflammatory effects of bAD-MSCs on LPS induced bEEC inflammation, we used a bAD-MSC/bEEC co-culture system. The results showed that bAD-MSC treatments could significantly decrease LPS induced bEEC apoptosis and pro-inflammatory cytokine expression levels, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Furthermore, our results showed that bAD-MSC treatments could also significantly downregulate LPS induced p38, IkB-a, and JAK1 phosphorylation and Bax protein expression levels, which are closely related to inflammatory progress and cellular apoptosis in bEECs. Our findings demonstrate that bAD-MSCs play an inhibitory role in LPS induced bEEC inflammation and provide new insights for the clinical therapy of endometritis in dairy cows.

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          Most cited references55

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          Multilineage cells from human adipose tissue: implications for cell-based therapies.

          Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.
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            Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?

            Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.
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              The regulation of IL-10 production by immune cells.

              Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a central role in infection by limiting the immune response to pathogens and thereby preventing damage to the host. Recently, an increasing interest in how IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation. Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                21 October 2021
                2021
                : 8
                : 726328
                Affiliations
                [1] 1Laboratory of Theriogenology and Reproductive Health, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University , Daqing, China
                [2] 2Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University , Daqing, China
                [3] 3Laboratory of Stem Cell Therapy and Regenration Biology, College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University , Daqing, China
                [4] 4Cofeed Feedmill (Changchun) Co., Ltd. , Changchun, China
                Author notes

                Edited by: Tereza Cristina Cardoso, Universidade Estadual de São Paulo, Brazil

                Reviewed by: Andrea Verna, Instituto Nacional de Tecnología Agropecuaria, Argentina; Oscar Peralta, University of Chile, Chile

                *Correspondence: Ying-Hao Han hyhbynd@ 123456163.com

                This article was submitted to Animal Reproduction - Theriogenology, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2021.726328
                8567161
                34746277
                17677aca-fb08-44c9-a81c-ef7889beedc9
                Copyright © 2021 Lu, Xu, Liu, Yu, Yu, Li, Mao, Du, Si, Yuan, Jin, Fu, Sun and Han.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 June 2021
                : 29 September 2021
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 55, Pages: 11, Words: 7308
                Funding
                Funded by: Natural Science Foundation of Heilongjiang Province, doi 10.13039/501100005046;
                Categories
                Veterinary Science
                Original Research

                bovine adipose-derived mesenchymal stem cell,inflammation,lipopolysaccharide,endometritis,dairy cows

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