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      Drug Design, Development and Therapy (submit here)

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      Umbilical Cord Mesenchymal Stem Cell Therapy for Regenerative Treatment of Rheumatoid Arthritis: Opportunities and Challenges

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          Abstract

          Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.

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          Most cited references66

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          Mesenchymal Stem Cell Migration and Tissue Repair

          Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs—namely, directed differentiation and the paracrine function—in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.
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            The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine

            Menstrual blood-derived stem cells (MenSCs) are a novel source of mesenchymal stem cells (MSCs). MenSCs are attracting more and more attention since their discovery in 2007. MenSCs also have no moral dilemma and show some unique features of known adult-derived stem cells, which provide an alternative source for the research and application in regenerative medicine. Currently, people are increasingly interested in their clinical potential due to their high proliferation, remarkable versatility, and periodic acquisition in a non-invasive manner with no other sources of MSCs that are comparable in adult tissue. In this review, the plasticity of pluripotent biological characteristics, immunophenotype and function, differentiative potential, and immunomodulatory properties are assessed. Furthermore, we also summarize their therapeutic effects and functional characteristics in various diseases, including liver disease, diabetes, stroke, Duchenne muscular dystrophy, ovarian-related disease, myocardial infarction, Asherman syndrome, Alzheimer’s disease, acute lung injury, cutaneous wound, endometriosis, and neurodegenerative diseases. Subsequently, the clinical potential of MenSCs is investigated. There is a need for a deeper understanding of its immunomodulatory and diagnostic properties with safety concern on a variety of environmental conditions (such as epidemiological backgrounds, age, hormonal status, and pre-contraceptive). In summary, MenSC has a great potential for reducing mortality and improving the quality of life of severe patients. As a kind of adult stem cells, MenSCs have multiple properties in treating a variety of diseases in regenerative medicine for future clinical applications.
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              Concise Review: Mesenchymal Stem Cells: From Roots to Boost

              It was shown as long as half a century ago that bone marrow is a source of not only hematopoietic stem cells, but also stem cells of mesenchymal tissues. Then the term "mesenchymal stem cells" (MSCs) was coined in the early 1990s, and more than a decade later, the criteria for defining MSCs have been released by the International Society for Cellular Therapy. The easy derivation from a variety of fetal and adult tissues and undemanding cell culture conditions made MSCs an attractive research object. It was followed by the avalanche of reports from preclinical studies on potentially therapeutic properties of MSCs, such as immunomodulation, trophic support and capability for a spontaneous differentiation into connective tissue cells, and differentiation into the majority of cell types upon specific inductive conditions. Although ontogenesis, niche, and heterogeneity of MSCs are still under investigation, there is a rapid boost of attempts at clinical applications of MSCs, especially for a flood of civilization-driven conditions in so quickly aging societies, not only in the developed countries, but also in the populous developing world. The fields of regenerative medicine and oncology are particularly extensively addressed by MSC applications, in part due to the paucity of traditional therapeutic options for these highly demanding and costly conditions. There are currently almost 1,000 clinical trials registered worldwide at ClinicalTrials.gov, and it seems that we are starting to witness the snowball effect with MSCs becoming a powerful global industry; however, the spectacular effects of MSCs in the clinic still need to be shown. Stem Cells 2019;37:855-864.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                15 September 2021
                2021
                : 15
                : 3927-3936
                Affiliations
                [1 ]Department of Laboratory Medicine, Liuzhou Maternity and Child Healthcare Hospital , Liu Zhou, Guang Xi, People’s Republic of China
                [2 ]Shaanxi Jiuzhou Biomedical Science and Technology Group , Xi’an, Shaan Xi, People’s Republic of China
                [3 ]Department of Hematology, 986 Hospital of Fourth Military Medical University , Xi’an, Shaan Xi, People’s Republic of China
                [4 ]Faculty of Health Sciences, University of Macau , Macau, People’s Republic of China
                Author notes
                Correspondence: Shigao Huang Email huangshigao2010@aliyun.com
                [*]

                These authors contributed equally to this work

                Author information
                https://orcid.org/http://orcid.org/0000-0002-9157-9964
                Article
                323107
                10.2147/DDDT.S323107
                8462093
                34584402
                d8e5af39-de93-4f16-8c8a-a10427c55026
                © 2021 Lv et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 03 June 2021
                : 26 August 2021
                Page count
                Figures: 1, Tables: 3, References: 66, Pages: 10
                Funding
                Funded by: Guangxi Zhuang Autonomous Region self-funded project;
                Funded by: the Project of Liuzhou Science and Technology Bureau;
                This research was supported by the Guangxi Zhuang Autonomous Region self-funded project (NO: Z20190359) and the Project of Liuzhou Science and Technology Bureau (No: 2018BJ10502).
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                cell-based therapies,rheumatoid arthritis,mesenchymal stem cells,umbilical cord,regenerative medicine

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