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      hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System

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          Abstract

          The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. Here, an hTERT-BMSCs/Tet-on/GAL cell line was constructed using a single Tet-on-inducible lentivirus system, and subsequent experiments demonstrated that the secretion of rat GAL from hTERT-BMSCs/Tet-on/GAL was switched on and off under the control of an inducer in a dose-dependent manner. The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain.

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          Aging of mesenchymal stem cell in vitro

          Mandana Mohyeddin Bonab, Kamran Alimoghaddam, Fatemeh Talebian … (2006)
          Background A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells. Results The mean long term culture was 118 days and the mean passage number was 9. The average number of PD decreased from 7.7 to 1.2 in the 10th passage. The mean telomere length decreased from 9.19 Kbp to 8.7 kbp in the 9th passage. Differentiation potential dropped from the 6th passage on. The culture's morphological abnormalities were typical of the Hayflick model of cellular aging. Conclusion We believe that MSC enter senescence almost undetectably from the moment of in vitro culturing. Simultaneously these cells are losing their stem cell characteristics. Therefore, it is much better to consider them for cell and gene therapy early on.
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            Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion.

            Melissa A Baxter, Robert Wynn, Simon Jowitt … (2004)
            Human marrow stromal cells (MSCs) can be isolated from bone marrow and differentiate into multiple tissues in vitro and in vivo. These properties make them promising tools in cell and gene therapy. The lack of a specific MSC marker and the low frequency of MSCs in bone marrow necessitate their isolation by in vitro expansion prior to clinical use. This may severely reduce MSC proliferative capacity to the point that the residual proliferative potential is insufficient to maintain long-term tissue regeneration upon reinfusion. In this study we determined the effect of in vitro expansion on the replicative capacity of MSCs by correlating their rate of telomere loss during in vitro expansion with their behavior in vivo. We report that even protocols that involve minimal expansion induce a rapid aging of MSCs, with losses equivalent to about half their total replicative lifespan.
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              Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.

              M Gossen, H Bujard (1992)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Stem Cells Int
                Journal ID (iso-abbrev): Stem Cells Int
                Journal ID (publisher-id): SCI
                Title: Stem Cells International
                Publisher: Hindawi
                ISSN (Print): 1687-966X
                ISSN (Electronic): 1687-9678
                Publication date (Print): 2017
                Publication date (Electronic): 11 May 2017
                Volume: 2017
                Electronic Location Identifier: 6082684
                Affiliations
                1Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
                2Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha 410013, China
                3Laboratory of Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
                4Department of Anesthesiology, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
                Author notes

                Academic Editor: Veronica Ramos-Mejia

                Author information
                http://orcid.org/0000-0001-8369-6557
                Article
                DOI: 10.1155/2017/6082684
                PMC ID: 5444038
                PubMed ID: 28584529
                SO-VID: c4985de1-8133-4101-b063-7161b31ad28f
                Copyright © Copyright © 2017 Ke An et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 21 November 2016
                Date revision received : 26 January 2017
                Date accepted : 22 February 2017
                Funding
                Funded by: Research Fund for the Doctoral Program of Higher Education of China
                Award ID: 20080558112
                Funded by: National Natural Science Foundation of China
                Award ID: 81171468
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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