8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Isolation, Characterization, Differentiation and Immunomodulatory Capacity of Mesenchymal Stromal/Stem Cells from Human Perirenal Adipose Tissue

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mesenchymal stromal/stem cells (MSCs) are immature multipotent cells, which represent a rare population in the perivascular niche within nearly all tissues. The most abundant source to isolate MSCs is adipose tissue. Currently, perirenal adipose tissue is rarely described as the source of MSCs. MSCs were isolated from perirenal adipose tissue (prASCs) from patients undergoing tumor nephrectomies, cultured and characterized by flow cytometry and their differentiation potential into adipocytes, chondrocytes, osteoblasts and epithelial cells. Furthermore, prASCs were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA) or a mixture of cytokines (cytomix). In addition, prASC susceptibility to human cytomegalovirus (HCMV) was investigated. The expression of inflammatory readouts was estimated by qPCR and immunoassay. HCMV infection was analyzed by qPCR and immunostaining. Characterization of cultured prASCs shows the cells meet the criteria of MSCs and prASCs can undergo trilineage differentiation. Cultured prASCs can be induced to differentiate into epithelial cells, shown by cytokeratin 18 expression. Stimulation of prASCs with LPS or cytomix suggests the cells are capable of initiating an inflammation-like response upon stimulation with LPS or cytokines, whereas, LTA did not induce a significant effect on the readouts (ICAM-1, IL-6, TNFα, MCP-1 mRNA and IL-6 protein). HCMV broadly infects prASCs, showing a viral load dependent cytopathological effect (CPE). Our current study summarizes the isolation and culture of prASCs, clearly characterizes the cells, and demonstrates their immunomodulatory potential and high permissiveness for HCMV.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Mesenchymal Stem Cells for Regenerative Medicine

          In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Toll-like receptors in the pathogenesis of human disease.

            Members of the Toll-like receptor (TLR) family are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated by comparison of the incidence of disease among people having different polymorphisms in genes that participate in TLR signaling. These studies have shown that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis and asthma. As this body of data grows, it will provide new insights into disease pathogenesis as well as valuable information on the merits of various therapeutic options.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells.

              Mesenchymal stromal cells (MSC) are involved in tissue repair and in the regulation of immune responses. MSC express Toll-like receptors (TLR) known to link innate and adaptive immunity. We hypothesized that TLR signaling could influence human MSC (hMSC) function. Here, we show that hMSC express TLR1, TLR2, TLR3, TLR4, TLR5, and TLR6 but not TLR7, TLR8, TLR9, and TLR10. In inflammatory conditions mimicked by culturing hMSC in an inflammatory environment, TLR2, TLR3, and TLR4 are upregulated, whereas TLR6 is downregulated. Interleukin (IL)-1 beta, IL-6, IL-12p35 and transforming growth factor-beta mRNAs are constitutively expressed by hMSC. Inflammation leads to an increase in IL-1 beta, IL-6, IL-12p35, and transforming growth factor-beta transcription and is characterized by IL-23p19 and IL-27p28 transcription. In this setting, poly(I:C) further augments IL-6, IL-12p35, IL-23p19, and IL-27p28 transcription, whereas lipopolysaccharide (LPS) increases IL-23p19 and IL-27p28 transcription. By upregulating TLR3 and TLR4 transcription, inflammation increases the hMSC responsiveness to LPS and poly(I:C), leading to a proinflammatory shift in their cytokine profile. The hMSC osteogenic potential does not change after TLR triggering but stimulation with LPS and poly(I:C) results in a decrease in their immunosuppressive capabilities. In conclusion, TLR activation in hMSC may affect their function and could modify their in vivo fate, especially in an inflammatory context. (c) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                29 October 2019
                November 2019
                : 8
                : 11
                : 0
                Affiliations
                [1 ]Division of Nephrology, Department of Internal Medicine III, University Hospital, Goethe University, 60596 Frankfurt/M., Germany; b.koch@ 123456med.uni-frankfurt.de (B.K.); elena.hickmann@ 123456gmx.de (E.H.); ingeborg.hauser@ 123456kgu.de (I.A.H.); h.geiger@ 123456em.uni-frankfurt.de (H.G.)
                [2 ]Division of Allergology, Pneumology and Cystic Fibrosis, Department for Children and Adolescents, University Hospital, Goethe University, 60596 Frankfurt/M., Germany; ralf.schubert@ 123456kgu.de
                [3 ]Institute of Medical Virology, University Hospital, Goethe University, 60596 Frankfurt/M., Germany; cinatl@ 123456em.uni-frankfurt.de
                Author notes
                [* ]Correspondence: patrick.baer@ 123456kgu.de or p.baer@ 123456em.uni-frankfurt.de ; Tel.: +49-69-6301-5554; Fax: +49-69-6301-4749
                [†]

                These authors contributed equally to this paper.

                Author information
                https://orcid.org/0000-0001-8113-3312
                https://orcid.org/0000-0002-3253-8396
                Article
                cells-08-01346
                10.3390/cells8111346
                6928994
                31671899
                76374800-cef4-444f-b334-94742f7c99d9
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 October 2019
                : 29 October 2019
                Categories
                Article

                mesenchymal stromal/stem cells,perirenal,adipose tissue,fat,characterization,stimulation,lipopolysaccharide,cytokines,cytomegalovirus

                Comments

                Comment on this article