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      Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

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          Abstract

          Various diseases and toxic factors easily impair cellular and organic functions in mammals. Organ transplantation is used to rescue organ function, but is limited by scarce resources. Mesenchymal stem cell ( MSC)‐based therapy carries promising potential in regenerative medicine because of the self‐renewal and multilineage potency of MSCs; however, MSCs may lose biological functions after isolation and cultivation for a long time in vitro. Moreover, after they are injected in vivo and migrate into the damaged tissues or organs, they encounter a harsh environment coupled with death signals due to the inadequate tensegrity structure between the cells and matrix. Preconditioning, genetic modification and optimization of MSC culture conditions are key strategies to improve MSC functions in vitro and in vivo, and all of these procedures will contribute to improving MSC transplantation efficacy in tissue engineering and regenerative medicine. Preconditioning with various physical, chemical and biological factors is possible to preserve the stemness of MSCs for further application in studies and clinical tests. In this review, we mainly focus on preconditioning and the corresponding mechanisms for improving MSC activities in vitro and in vivo; we provide a glimpse into the promotion of MSC‐based cell therapy development for regenerative medicine. As a promising consequence, MSC transplantation can be applied for the treatment of some terminal diseases and can prolong the survival time of patients in the near future.

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          Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?

          Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.
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            Mesenchymal Stromal Cells: Current Understanding and Clinical Status

            Multipotent mesenchymal stromal cells (MSCs) represent a rare heterogeneous subset of pluripotent stromal cells that can be isolated from many different adult tissues that exhibit the potential to give rise to cells of diverse lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After culture expansion and in vivo administration, MSCs home to and engraft to injured tissues and modulate the inflammatory response through synergistic downregulation of proinflammatory cytokines and upregulation of both prosurvival and antiinflammatory factors. In addition, MSCs possess remarkable immunosuppressive properties, suppressing T-cell, NK cell functions, and also modulating dentritic cell activities. Tremendous progress has been made in preclinical studies using MSCs, including the ability to use allogeneic cells, which has driven the application of MSCs toward the clinical setting. This review highlights our current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of MSC-based therapy.
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              A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods

              The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions.
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                Author and article information

                Contributors
                ljli@zju.edu.cn
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                01 February 2018
                March 2018
                : 22
                : 3 ( doiID: 10.1111/jcmm.2018.22.issue-3 )
                : 1428-1442
                Affiliations
                [ 1 ] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases School of Medicine First Affiliated Hospital Zhejiang University Hangzhou Zhejiang China
                Author notes
                [*] [* ] Correspondence to: Lanjuan LI

                E‐mail: ljli@ 123456zju.edu.cn

                Author information
                http://orcid.org/0000-0001-7106-128X
                Article
                JCMM13492
                10.1111/jcmm.13492
                5824372
                29392844
                d45bf5b2-db08-470d-b23e-6174fd93591b
                © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

                History
                : 09 August 2017
                : 31 October 2017
                Page count
                Figures: 2, Tables: 2, Pages: 15, Words: 10539
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81700553
                Funded by: Stem Cell and Translational Research, the National Key Research and Development Program of China
                Award ID: 2016YFA0101001
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2017M183789
                Funded by: Science Fund for Creative Research Groups of the National Natural Science Foundation of China
                Award ID: 81121002
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                jcmm13492
                March 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:23.02.2018

                Molecular medicine
                preconditioning,mesenchymal stem cell,stemness,in vitro,in vivo
                Molecular medicine
                preconditioning, mesenchymal stem cell, stemness, in vitro, in vivo

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