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      Osteogenic Differentiation of Late-Outgrowth CD45-Negative Endothelial Progenitor Cells

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          Abstract

          Background/Aims: Late-outgrowth CD45-negative endothelial colony-forming cells are implicated to be circulating endothelial progenitor cells (EPCs), as they express endothelial cell markers and can directly form blood vessels. As these cells share characteristics of other progenitor cell phenotypes, late-outgrowth EPCs were assayed for both multilineage differentiation capability and for markers of pluripotency. Methods: Clonal single-colony late-outgrowth EPCs were derived from human cord blood and assayed both for multilineage differentiation capability in vitro and for markers of pluripotency by qPCR. Results: Under osteogenic growth conditions, these EPCs expressed the osteogenic markers RUNX2, COL1A1, ALPL, and osteocalcin and demonstrated calcium deposition and bone mineralization. Endothelial colony-forming cells expressed markers associated with induced pluripotent stem cells, including SOX2, POU5F1, c-MYC, and KLF4. Conclusions: Late-outgrowth EPCs express markers associated with pluripotency and can directly express an osteogenic phenotype under bone differentiation conditions in vitro. i 2014 S. Karger AG, Basel

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          Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.

          Mervin C. Yoder, Laura Mead, Daniel Prater … (2006)
          The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.
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            Forcing cells to change lineages.

            Thomas Graf, Tariq Enver (2009)
            The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.
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              Conversion of vascular endothelial cells into multipotent stem-like cells.

              Damian Medici, Eileen Shore, Vitali Y Lounev … (2010)
              Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2 (ALK2) receptor-dependent mechanism. In lesions from individuals with fibrodysplasia ossificans progressiva (FOP), a disease in which heterotopic ossification occurs as a result of activating ALK2 mutations, or from transgenic mice expressing constitutively active ALK2, chondrocytes and osteoblasts expressed endothelial markers. Lineage tracing of heterotopic ossification in mice using a Tie2-Cre construct also suggested an endothelial origin of these cell types. Expression of constitutively active ALK2 in endothelial cells caused endothelial-to-mesenchymal transition and acquisition of a stem cell-like phenotype. Similar results were obtained by treatment of untransfected endothelial cells with the ligands transforming growth factor-β2 (TGF-β2) or bone morphogenetic protein-4 (BMP4) in an ALK2-dependent manner. These stem-like cells could be triggered to differentiate into osteoblasts, chondrocytes or adipocytes. We suggest that conversion of endothelial cells to stem-like cells may provide a new approach to tissue engineering.
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                Author and article information

                Journal
                Journal ID (publisher-id): JVR
                Journal ID (nlm-ta): J Vasc Res
                Journal ID (doi): 10.1159/issn.1018-1172
                Title: Journal of Vascular Research
                Publisher: S. Karger AG
                ISSN (Print): 1018-1172
                ISSN (Electronic): 1423-0135
                Publication date Subscription-year: 2014
                Publication date (Print): January 2015
                Publication date (Electronic): 12 December 2014
                Volume: 51
                Issue: 5
                Pages: 369-375
                Affiliations
                aDepartment of Pathobiology, Lerner Research Institute, and bDepartment of Allergy and Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
                Author notes
                *Dr. Fred H. Hsieh, Department of Allergy and Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195 (USA), E-Mail Hsiehf@ccf.org
                Article
                Publisher ID: 368929 Other ID: J Vasc Res 2014;51:369-375
                DOI: 10.1159/000368929
                PubMed ID: 25531767
                SO-VID: d2f64756-6f09-434f-b267-3901f13d71dd
                Copyright © © 2014 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 06 February 2014
                Date accepted : 30 September 2014
                Page count
                Figures: 2, References: 17, Pages: 7
                Categories
                Subject: Short Communication

                ScienceOpen disciplines: General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Keywords: Multipotency,Osteogenesis,Endothelial colony-forming cell,Endothelial progenitor cell,Differentiation,Lineage
                Data availability:
                ScienceOpen disciplines: General medicine, Neurology, Cardiovascular Medicine, Internal medicine, Nephrology
                Keywords: Multipotency, Osteogenesis, Endothelial colony-forming cell, Endothelial progenitor cell, Differentiation, Lineage

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