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      Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

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          Abstract

          Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.

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

          M Dominici, K Le Blanc, I. Mueller … (2006)
          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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            The biology and function of fibroblasts in cancer.

            Raghu Kalluri (2016)
            Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.
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              Neutrophil recruitment and function in health and inflammation.

              Elzbieta Kolaczkowska, Paul Kubes (2013)
              Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Bioeng Biotechnol
                Journal ID (iso-abbrev): Front Bioeng Biotechnol
                Journal ID (publisher-id): Front. Bioeng. Biotechnol.
                Title: Frontiers in Bioengineering and Biotechnology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-4185
                Publication date (Electronic): 05 February 2020
                Publication date Collection: 2020
                Volume: 8
                Electronic Location Identifier: 43
                Affiliations
                [1] 1Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Pablo de Olavide University, University of Seville, CSIC , Seville, Spain
                [2] 2Biomedical Research Network on Diabetes and Related Metabolic Diseases (CIBERDEM), Institute of Health Carlos III , Madrid, Spain
                [3] 3School of Medicine , Miguel Hernández University, Alicante, Spain
                [4] 4Pablo de Olavide University , Seville, Spain
                Author notes

                Edited by: Hugo Guerrero-Cazares, Mayo Clinic, United States

                Reviewed by: Rajendra K. Singh, Institute of Tissue Regeneration Engineering (ITREN), South Korea; Lia Rimondini, University of Eastern Piedmont, Italy

                *Correspondence: Abdelkrim Hmadcha, khmadcha@ 123456upo.es
                Vivian Capilla-González, vivian.capilla@ 123456cabimer.es

                †Lead contact

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                DOI: 10.3389/fbioe.2020.00043
                PMC ID: 7013101
                PubMed ID: 32117924
                SO-VID: ab39be7b-6539-4496-a125-56c14ef7c088
                Copyright © Copyright © 2020 Hmadcha, Martin-Montalvo, Gauthier, Soria and Capilla-Gonzalez.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 27 November 2019
                Date accepted : 21 January 2020
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 135, Pages: 13, Words: 0
                Categories
                Subject: Bioengineering and Biotechnology
                Subject: Review

                Keywords: mesenchymal stem cells,cancer,cell therapy,therapeutic agents,anti-tumor activity
                Data availability:
                Keywords: mesenchymal stem cells, cancer, cell therapy, therapeutic agents, anti-tumor activity

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