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      Ginsenoside Rg1 as an Effective Regulator of Mesenchymal Stem Cells

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          Abstract

          Recently, breakthroughs have been made in the use of mesenchymal stem cells (MSCs) to treat various diseases. Several stem cell types have been authorized as drugs by the European Medicines Agency and the U.S. Food and Drug Administration. The Chinese official document “Notification of the management of stem cell clinical research (trial)” was also published in August 2015. Currently, China has approved 106 official stem cell clinical research filing agencies and 62 clinical research projects, which are mostly focused on MSC therapy. Hence, the optimization and development of stem cell drugs is imperative. During this process, maximizing MSC expansion, minimizing cell loss during MSC transplantation, improving the homing rate, precisely regulating the differentiation of MSCs, and reducing MSC senescence and apoptosis are major issues in MSC preclinical research. Similar to artemisinin extracted from the stems and leaves of Artemisia annua, ginsenoside Rg1 (Rg1) is purified from the root or stem of ginseng. In the human body, Rg1 regulates organ function, which is inseparable from its regulation of adult stem cells. Rg1 treatment may effectively regulate the proliferation, differentiation, senescence, and apoptosis of MSCs in different microenvironments in vitro or in vivo. In this review, we discuss recent advances in understanding the effect of Rg1 on MSCs and describe the issues that must be addressed and prospects regarding Rg1 regulation of MSCs in preclinical or clinical studies.

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          Most cited references83

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          Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

          Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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            Concise Review: MSC-Derived Exosomes for Cell-Free Therapy.

            Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.
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              Bone-marrow haematopoietic-stem-cell niches.

              Adult stem cells hold many promises for future clinical applications and regenerative medicine. The haematopoietic stem cell (HSC) is the best-characterized somatic stem cell so far, but in vitro expansion has been unsuccessful, limiting the future therapeutic potential of these cells. Here we review recent progress in characterizing the composition of the HSC bone-marrow microenvironment, known as the HSC niche. During homeostasis, HSCs, and therefore putative bone-marrow HSC niches, are located near bone surfaces or are associated with the sinusoidal endothelium. The molecular crosstalk between HSCs and the cellular constituents of these niches is thought to control the balance between HSC self-renewal and differentiation, indicating that future successful expansion of HSCs for therapeutic use will require three-dimensional reconstruction of a stem-cell-niche unit.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                23 January 2020
                2019
                : 10
                : 1565
                Affiliations
                [1] 1 Key Laboratory of Cell Engineering of Guizhou Province, The Affiliated Hospital of Zunyi Medical University , Zunyi, China
                [2] 2 Department of Oral and Maxillofacial Surgery, University Hospital of Tübingen , Tübingen, Germany
                [3] 3 Department of Neurology, The Affiliated Hospital of Zunyi Medical University , Zunyi, China
                [4] 4 School of Stomatology, Xi’an Medical University , Xi’an, China
                Author notes

                Edited by: Vincent Kam Wai, Macau University of Science and Technology, Macau

                Reviewed by: Patrick Ying Kit Yue, Hong Kong Baptist University, Hong Kong; Qiang Wu, Macau University of Science and Technology, Macau

                *Correspondence: Fang He, hfwyyx@ 123456yeah.net ; Changyin Yu, ycynerve@ 123456163.com ; Tao Liu, ltcells@ 123456163.com

                †These authors share first authorship

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.01565
                6989539
                32038244
                c0b97d58-c9e8-444a-a233-407e22823465
                Copyright © 2020 He, Yu, Liu and Jia

                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
                : 21 August 2019
                : 03 December 2019
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 100, Pages: 12, Words: 5564
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                ginsenoside rg1,mesenchymal stem cells,proliferation,differentiation,apoptosis,senescence,preclinical study

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