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      Comparative analysis of human Wharton’s jelly mesenchymal stem cells derived from different parts of the same umbilical cord

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          Abstract

          Easy isolation, lack of ethical issues, high proliferation, multi-lineage differentiation potential and immunomodulatory properties of umbilical cord (UC)-derived mesenchymal stem cells (MSCs) make them a valuable tool in stem cell research. Recently, Wharton’s jelly (WJ) was proven as the best MSC source among various compartments of UC. However, it is still unclear whether or not Wharton’s jelly-derived MSCs (WJMSCs) from different parts of the whole cord exhibit the same characteristics. There may be varied MSCs present in different parts of WJ throughout the length of the UC. For this purpose, using an explant attachment method, WJMSCs were isolated from three different parts of the UC, mainly present towards the placenta (mother part), the center of the whole cord (central part) and the part attached to the fetus (baby part). WJMSCs from all three parts were maintained in normal growth conditions (10% ADMEM) and analyzed for mesenchymal markers, pluripotent genes, proliferation rate and tri-lineage differentiation potential. All WJMSCs were highly proliferative, positively expressed CD90, CD105, CD73 and vimentin, while not expressing CD34, CD45, CD14, CD19 or HLA-DR, differentiated into adipocytes, osteocytes and chondrocytes and expressed pluripotency markers OCT-4, SOX-2 and NANOG at gene and protein levels. Furthermore, MSCs derived from all the parts were shown to have potency towards hepatocyte-like cell differentiation. Human bone marrow-derived MSCs were used as a positive control. Finally, we conclude that WJMSCs derived from all the parts are valuable sources and can be efficiently used in various fields of regenerative medicine.

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          The online version of this article (10.1007/s00441-017-2699-4) contains supplementary material, which is available to authorized users.

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

          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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            The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.

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              Is Open Access

              Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications

              Wharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
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                Author and article information

                Contributors
                jinrho@gnu.ac.kr
                Journal
                Cell Tissue Res
                Cell Tissue Res
                Cell and Tissue Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0302-766X
                1432-0878
                4 December 2017
                4 December 2017
                2018
                : 372
                : 1
                : 51-65
                Affiliations
                [1 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, Department of Theriogenology and Biotechnology, College of Veterinary Medicine, , Gyeongsang National University, ; Jinju, Republic of Korea
                [2 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, Department of Obstetrics and Gynecology, School of Medicine, , Gyeongsang National University, ; Jinju, Republic of Korea
                [3 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, Department of Oral and Maxillofacial Surgery, School of Medicine, , Gyeongsang National University, ; Jinju, Republic of Korea
                [4 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, Research Institute of Life Sciences, , Gyeongsang National University, ; Jinju, Republic of Korea
                Article
                2699
                10.1007/s00441-017-2699-4
                5862947
                29204746
                8d527063-1aec-46c7-be08-0db465ea7280
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 15 November 2016
                : 11 September 2017
                Funding
                Funded by: Korea Health Industry Development Institute (KHIDI), Ministry of Health & Welfare, Republic of Korea
                Award ID: grant number : H113C1596
                Categories
                Regular Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Molecular medicine
                transdifferentiation,hepatocytes,mesenchymal stem cells,wharton’s jelly,umbilical cord

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