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      Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine

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          Abstract

          Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth factors, cytokines, and extracellular vesicles, can repair the injured tissues as effectively as the cells. This finding has spurred a new idea to employ secretome in regenerative medicine. Despite that, will cell-free therapy slowly replace cell therapy in the future? Or are these two modes of treatment still needed to address different diseases and conditions? This review provides an indepth discussion about the values of stem cells and secretome in regenerative medicine. In addition, the safety, efficacy, advantages, and disadvantages of using these two modes of treatment in regenerative medicine are also critically reviewed.

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          Most cited references289

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

            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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              Matrix elasticity directs stem cell lineage specification.

              Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                sci
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2021
                19 August 2021
                : 2021
                : 2616807
                Affiliations
                1School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, 47500 Subang Jaya, Selangor, Malaysia
                2Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor's University, 47500 Subang Jaya, Selangor, Malaysia
                3My Cytohealth Sdn Bhd, Bandar Seri Petaling, 57000 Kuala Lumpur, Malaysia
                4National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
                5Institute of Medical Science Technology, Universiti Kuala Lumpur, 43000 Kajang, Selangor, Malaysia
                6Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Kuala Lumpur, Malaysia
                7School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia
                8School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, 47500 Subang Jaya, Malaysia
                Author notes

                Academic Editor: Kar Wey Yong

                Author information
                https://orcid.org/0000-0001-9045-5145
                Article
                10.1155/2021/2616807
                8378970
                34422061
                5fdb43a5-f269-463b-8d16-875cdd949d9d
                Copyright © 2021 Jhi Biau Foo et al.

                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
                : 14 May 2021
                : 28 July 2021
                Funding
                Funded by: Ministry of Higher Education, Malaysia
                Award ID: FRGS/1/2020/SKK0/UKM/02/5
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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