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      Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells

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          Abstract

          The umbilical cord has become an increasingly used source of mesenchymal stromal cells for preclinical and, more recently, clinical studies. Despite the increased activity, several aspects of this cell population have been under‐appreciated. Key issues are that consensus on the anatomical structures within the cord is lacking, and potentially different populations are identified as arising from a single source. To help address these points, we propose a histologically based nomenclature for cord structures and provide an analysis of their developmental origins and composition. Methods of cell isolation from Wharton's jelly are discussed and the immunophenotypic and clonal characteristics of the cells are evaluated. The perivascular origin of the cells is also addressed. Finally, clinical trials with umbilical cord cells are briefly reviewed. Interpreting the outcomes of the many clinical studies that have been undertaken with mesenchymal stromal cells from different tissue sources has been challenging, for many reasons. It is, therefore, particularly important that as umbilical cord cells are increasingly deployed therapeutically, we strive to better understand the derivation and functional characteristics of the cells from this important tissue source. S tem C ells T ranslational M edicine 2017;6:1620–1630

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

            Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging.
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              A perivascular origin for mesenchymal stem cells in multiple human organs.

              Mesenchymal stem cells (MSCs), the archetypal multipotent progenitor cells derived in cultures of developed organs, are of unknown identity and native distribution. We have prospectively identified perivascular cells, principally pericytes, in multiple human organs including skeletal muscle, pancreas, adipose tissue, and placenta, on CD146, NG2, and PDGF-Rbeta expression and absence of hematopoietic, endothelial, and myogenic cell markers. Perivascular cells purified from skeletal muscle or nonmuscle tissues were myogenic in culture and in vivo. Irrespective of their tissue origin, long-term cultured perivascular cells retained myogenicity; exhibited at the clonal level osteogenic, chondrogenic, and adipogenic potentials; expressed MSC markers; and migrated in a culture model of chemotaxis. Expression of MSC markers was also detected at the surface of native, noncultured perivascular cells. Thus, blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.
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                Author and article information

                Contributors
                jed.davies@utoronto.ca
                Journal
                Stem Cells Transl Med
                Stem Cells Transl Med
                10.1002/(ISSN)2157-6580
                SCT3
                Stem Cells Translational Medicine
                John Wiley and Sons Inc. (Hoboken )
                2157-6564
                2157-6580
                10 May 2017
                July 2017
                : 6
                : 7 ( doiID: 10.1002/sct3.2017.6.issue-7 )
                : 1620-1630
                Affiliations
                [ 1 ] Institute of Biomaterials and Biomedical Engineering Toronto Ontario Canada
                [ 2 ] Faculty of Dentistry University of Toronto Toronto Ontario Canada
                [ 3 ] Anatomy & Cell Biology Schulich School of Medicine and Dentistry, The University of Western Ontario London Ontario Canada
                [ 4 ] Cell Therapy Program, Arthritis Program, Krembil Research Institute, and Princess Margaret Cancer Centre, University Health Network Toronto Canada
                Author notes
                [*] [* ]Correspondence: John E. Davies B.D.S., Ph.D., D.Sc., Institute of Biomaterials and Biomedical Engineering, Rosebrugh Building, 164 College Street, Toronto, Ontario, Canada M5S 3G9. Telephone: (416) 978‐1471; e‐mail: jed.davies@ 123456utoronto.ca
                Author information
                http://orcid.org/0000-0002-8733-0082
                Article
                SCT312154
                10.1002/sctm.16-0492
                5689772
                28488282
                c7cf5929-9037-40f6-9076-d6021232a77d
                © 2017 The Authors S tem C ells T ranslational M edicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 19 December 2016
                : 03 February 2017
                : 24 February 2017
                Page count
                Figures: 5, Tables: 2, Pages: 11, Words: 10515
                Categories
                Tissue‐specific Progenitor and Stem cells
                Perivascular Stem/Progenitor Cells
                Mesenchymal Stem Cells
                Tissue Specific Stem Cells
                Cord / Cord Blood Stem Cells (WJ‐MSCs)
                Clinical Application / Translation
                Clinical Trials
                Immunomodulation
                Inflammation / Inflammatory Disease
                Tissue‐Specific Progenitor and Stem Cells
                Translational Research Articles and Reviews
                Tissue‐Specific Progenitor and Stem Cells
                Custom metadata
                2.0
                sct312154
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.4.1 mode:remove_FC converted:09.11.2017

                wharton's jelly,mesenchymal stromal cell,embryology,therapy

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