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      Challenges and Controversies in Human Mesenchymal Stem Cell Therapy

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      Journal: Stem Cells International
      Publisher: Hindawi

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          Abstract

          Stem cell therapy is being intensely investigated within the last years. Expectations are high regarding mesenchymal stem cell (MSC) treatment in translational medicine. However, many aspects concerning MSC therapy should be profoundly defined. Due to a variety of approaches that are investigated, potential effects of stem cell therapy are not transparent. On the other hand, most results of MSC administration in vivo have confirmed their safety and showed promising beneficial outcomes. However, the therapeutic effects of MSC-based treatment are still not spectacular and there is a potential risk related to MSC applications into specific cell niche that should be considered in long-term observations and follow-up outcomes. In this review, we intend to address some problems and critically discuss the complex nature of MSCs in the context of their effective and safe applications in regenerative medicine in different diseases including graft versus host disease (GvHD) and cardiac, neurological, and orthopedic disorders.

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          Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.

          Farida Djouad, Pascale Plence, Claire Bony … (2003)
          Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth. We first showed in vitro that the murine C3H10T1/2 (C3) MSC line and primary MSCs exhibit immunosuppressive properties in mixed lymphocyte reaction. We demonstrated that this effect is mediated by soluble factors, secreted only on "activation" of MSCs in the presence of splenocytes. Moreover, the immunosuppression is mediated by CD8+ regulatory cells responsible for the inhibition of allogeneic lymphocyte proliferation. We then demonstrated that the C3 MSCs expressing the human bone morphogenetic protein 2 (hBMP-2) differentiation factor were not rejected when implanted in various allogeneic immunocompetent mice and were still able to differentiate into bone. Importantly, using a murine melanoma tumor model, we showed that the subcutaneous injection of B16 melanoma cells led to tumor growth in allogeneic recipients only when MSCs were coinjected. Although the potential side effects of immunosuppression induced by MSCs have to be considered in further clinical studies, the usefulness of MSCs for various therapeutic applications still remains of great interest.
          Article 0 comments Cited 299 times – based on 0 reviews     Review now
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            Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.

            Dimitrios Karussis, Clementine Karageorgiou, Adi Vaknin-Dembinsky … (2010)
            To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial. Patients  Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled. Intervention  After culture, a mean (SD) of 63.2 × 10(6) (2.5 × 10(6)) MSCs was injected intrathecally (n = 34) and intravenously (n = 14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). The main outcome measure was the recording of side effects. Follow-up (≤25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation. Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4(+)CD25(+) regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40(+), CD83(+), CD86(+), and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation. Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects. Trial Registration  clinicaltrials.gov Identifier: NCT00781872.
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              The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology.

              Lawrence J. Laslett, Peter Alagona, Bernard A Clark … (2012)
              The environment in which the field of cardiology finds itself has been rapidly changing. This supplement, an expansion of a report created for the Board of Trustees, is intended to provide a timely snapshot of the socio-economic, political, and scientific aspects of this environment as it applies to practice both in the United States and internationally. This publication should assist healthcare professionals looking for the most recent statistics on cardiovascular disease and the risk factors that contribute to it, drug and device trends affecting the industry, and how the practice of cardiology is changing in the United States. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
              Article 0 comments Cited 254 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Katarzyna Drela:
                ORCID: http://orcid.org/0000-0003-4744-1500
                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 Collection: 2019
                Publication date (Electronic): 9 April 2019
                Volume: 2019
                Electronic Location Identifier: 9628536
                Affiliations
                1NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
                2Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
                3Department of Orthopedics and Traumatology, 1st Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland
                Author notes

                Academic Editor: James A. Ankrum

                Author information
                http://orcid.org/0000-0003-2168-4328
                http://orcid.org/0000-0003-3205-5949
                http://orcid.org/0000-0001-6814-6127
                http://orcid.org/0000-0001-9799-5750
                http://orcid.org/0000-0003-2437-8908
                http://orcid.org/0000-0003-4744-1500
                Article
                DOI: 10.1155/2019/9628536
                PMC ID: 6481040
                PubMed ID: 31093291
                SO-VID: 4a927317-bbbe-41fe-94df-e6153339c899
                Copyright © Copyright © 2019 Barbara Lukomska 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 : 5 December 2018
                Date accepted : 12 March 2019
                Funding
                Funded by: NCR&D
                Award ID: STRATEGMED1/235773/19/NCBR/2016
                Award ID: STRATEGMED3/303570/7/NCBR/2017
                Categories
                Subject: Review Article

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

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