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      Multi-Lineage Differentiation of Human Umbilical Cord Wharton’s Jelly Mesenchymal Stromal Cells Mediates Changes in the Expression Profile of Stemness Markers

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          Abstract

          Wharton’s Jelly- derived Mesenchymal stem cells (WJ-MSCs) have gained interest as an alternative source of stem cells for regenerative medicine because of their potential for self-renewal, differentiation and unique immunomodulatory properties. Although many studies have characterized various WJ-MSCs biologically, the expression profiles of the commonly used stemness markers have not yet been addressed. In this study, WJ-MSCs were isolated and characterized for stemness and surface markers expression. Flow cytometry, immunofluorescence and qRT-PCR analysis revealed predominant expression of CD29, CD44, CD73, CD90, CD105 and CD166 in WJ-MSCs, while the hematopoietic and endothelial markers were absent. Differential expression of CD 29, CD90, CD105 and CD166 following adipogenic, osteogenic and chondrogenic induction was observed. Furthermore, our results demonstrated a reduction in CD44 and CD73 expressions in response to the tri-lineage differentiation induction, suggesting that they can be used as reliable stemness markers, since their expression was associated with undifferentiated WJ-MSCs only.

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          Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord.

          Hwai-Shi Wang, Shih-Chieh Hung, Shu-Tine Peng … (2004)
          The Wharton's jelly of the umbilical cord contains mucoid connective tissue and fibroblast-like cells. Using flow cytometric analysis, we found that mesenchymal cells isolated from the umbilical cord express matrix receptors (CD44, CD105) and integrin markers (CD29, CD51) but not hematopoietic lineage markers (CD34, CD45). Interestingly, these cells also express significant amounts of mesenchymal stem cell markers (SH2, SH3). We therefore investigated the potential of these cells to differentiate into cardiomyocytes by treating them with 5-azacytidine or by culturing them in cardiomyocyte-conditioned medium and found that both sets of conditions resulted in the expression of cardiomyocyte markers, namely N-cadherin and cardiac troponin I. We also showed that these cells have multilineage potential and that, under suitable culture conditions, are able to differentiate into cells of the adipogenic and osteogenic lineages. These findings may have a significant impact on studies of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering by helping to eliminate worrying ethical and technical issues.
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            Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation.

            William Tse, John Pendleton, Wendy Beyer … (2003)
            Marrow stromal cells (MSC) can differentiate into multiple mesenchymal tissues. To assess the feasibility of human MSC transplantation, we evaluated the in vitro immunogenicity of MSC and their ability to function as alloantigen presenting cells (APC). Human MSC were derived and used in mixed cell cultures with allogeneic peripheral blood mononuclear cells (PBMC). Expression of immunoregulatory molecules on MSC was analyzed by flow cytometry. An MSC-associated suppressive activity was analyzed using cell-proliferation assays and enzyme-linked immunoassays. MSC failed to elicit a proliferative response when cocultured with allogeneic PBMC, despite provision of a costimulatory signal delivered by an anti-CD28 antibody and pretreatment of MSC with gamma-interferon. MSC express major histocompatibility complex (MHC) class I and lymphocyte function-associated antigen (LFA)-3 antigens constitutively and MHC class II and intercellular adhesion molecule (ICAM)-1 antigens upon gamma-interferon treatment but do not express CD80, CD86, or CD40 costimulatory molecules. MSC actively suppressed proliferation of responder PBMC stimulated by third-party allogeneic PBMC as well as T cells stimulated by anti-CD3 and anti-CD28 antibodies. Separation of MSC and PBMC by a semipermeable membrane did not abrogate the suppression. The suppressive activity could not be accounted for by MSC production of interleukin-10, transforming growth factor-beta1, or prostaglandin E2, nor by tryptophan depletion of the culture medium. Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures. Unlike other nonprofessional APC, this failure of function is not reversed by provision of CD28-mediated costimulation nor gamma-interferon pretreatment. Rather, MSC actively inhibit T-cell proliferation, suggesting that allogeneic MSC transplantation might be accomplished without the need for significant host immunosuppression.
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              The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.

              R Chailakhjan, K S Lalykina, A Y Friedenstein (1970)
              Article 0 comments Cited 296 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zoran Ivanovic: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 7 April 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 4
                Electronic Location Identifier: e0122465
                Affiliations
                [1 ]Department of Basic Science Research, Dasman Diabetes Institute, 1180 Dasman, Kuwait
                [2 ]Department of Medical Laboratory Sciences (MLS), Faculty of Allied Health Sciences, Health Sciences Center, Kuwait University, Kuwait City, Kuwait
                [3 ]Dar Al Baraa Medical Center, 3357 Hawally, Kuwait
                [4 ]Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, 1180 Dasman, Kuwait
                French Blood Institute, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HA AAM. Performed the experiments: HA MAF AAM. Analyzed the data: HA KB AAM. Contributed reagents/materials/analysis tools: MKA KB AAM. Wrote the paper: AAM. Obtained permission for use of WJ-MSCs: KB AAM.

                Article
                Publisher ID: PONE-D-14-33205
                DOI: 10.1371/journal.pone.0122465
                PMC ID: 4388513
                PubMed ID: 25848763
                SO-VID: 5d10772d-57ce-455f-bbc1-ea8da7466362
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 24 July 2014
                Date accepted : 11 February 2015
                Page count
                Figures: 6, Tables: 2, Pages: 18
                Funding
                RA-2013-009 and 2012-1302-03, www.kfas.org, Kuwait Foundation for the Advancement of Sciences, for AAM and HA, respectively. OMICSRU grant SRUL02/13 for HA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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