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      Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study

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          Abstract

          Introduction

          Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.

          Methods

          Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 10 6 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up.

          Results

          No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment.

          Conclusion

          Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations.

          Trial registration

          ISRCTN, ISRCTN70443938. Registered 06 July 2019

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          Most cited references 53

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          Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives.

          Mesenchymal stem cells (MSCs) are one of a few stem cell types to be applied in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair. In addition to their multipotent differentiation potential, a strong paracrine capacity has been proposed as the principal mechanism that contributes to tissue repair. Apart from cytokine/chemokine secretion, MSCs also display a strong capacity for mitochondrial transfer and microvesicle (exosomes) secretion in response to injury with subsequent promotion of tissue regeneration. These unique properties of MSCs make them an invaluable cell type to repair damaged tissues/organs. Although MSCs offer great promise in the treatment of degenerative diseases and inflammatory disorders, there are still many challenges to overcome prior to their widespread clinical application. Particularly, their in-depth paracrine mechanisms remain a matter for debate and exploration. This review will highlight the discovery of the paracrine mechanism of MSCs, regulation of the paracrine biology of MSCs, important paracrine factors of MSCs in modulation of tissue repair, exosome and mitochondrial transfer for tissue repair, and the future perspective for MSC-based therapy.
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            Mesenchymal stem cells: mechanisms of inflammation.

            In adults, human mesenchymal stem cells (hMSCs) are found in vivo at low frequency and are defined by their capacity to differentiate into bone, cartilage, and adipose tissue, depending on the stimuli and culture conditions under which they are expanded. Although MSCs were initially hypothesized to be the panacea for regenerating tissues, MSCs appear to be more important in therapeutics to regulate the immune response invoked in settings such as tissue injury, transplantation, and autoimmunity. MSCs have been used therapeutically in clinical trials and subsequently in practice to treat graft-versus-host disease following bone marrow transplantation. Reports of successful immune modulation suggest efficacy in a wide range of autoimmune conditions, such as demyelinating neurological disease (multiple sclerosis), systemic lupus erythematosus, and Crohn's disease, among others. This review provides background information about hMSCs and also describes their putative mechanisms of action in inflammation. We provide a summary of ongoing clinical trials to allow (a) full comprehension of the range of diseases in which hMSC therapy may be beneficial and (b) identification of gaps in our knowledge about the mechanisms of action of therapeutic MSCs in disease.
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              Aging of mesenchymal stem cell in vitro

              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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                Author and article information

                Contributors
                drbphuong@gmail.com
                bshahohap@gmail.com
                hoangdcn4390@gmail.com
                pvtien.vhscun@gmail.com
                dobaquyet@yahoo.com
                hungdk688@gmail.com
                levandong@yahoo.com
                huyluca3bv103@gmail.com
                maixuankhan@gmail.com
                tabathang@yahoo.com
                dominhtrungut@yahoo.com
                Ngocvu@sci.edu.vn
                Nhattruong@sci.edu.vn
                pvphuc@hcmuns.edu.vn , phucpham@sci.edu.vn
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                13 February 2020
                13 February 2020
                2020
                : 11
                Affiliations
                [1 ]Van Hanh General Hospital, Ho Chi Minh City, Viet Nam
                [2 ]Vietnam Millitay Academy 103, Ha Noi, Viet Nam
                [3 ]GRID grid.454160.2, ISNI 0000 0004 0642 8526, Stem Cell Institute, , VNUHCM University of Science, ; Ho Chi Minh City, Viet Nam
                [4 ]GRID grid.454160.2, ISNI 0000 0004 0642 8526, Laboratory of Stem Cell Research and Application, , VNUHCM University of Science, ; Ho Chi Minh City, Viet Nam
                Article
                1583
                10.1186/s13287-020-1583-4
                7020576
                32054512
                © The Author(s). 2020

                Open AccessThis 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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100007225, Ministry of Science and Technology;
                Award ID: KC.10.15/16-20
                Award Recipient :
                Funded by: Ministry of Science and Technology, Vietnam
                Award ID: DM.10.DA/15
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

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