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      Freeze-dried and GMP-compliant pharmaceuticals containing exosomes for acellular mesenchymal stromal cell immunomodulant therapy

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          Most cited references 22

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          Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells.

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            Is Open Access

            Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

            Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.
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              Using exosomes, naturally-equipped nanocarriers, for drug delivery.

              Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.
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                Author and article information

                Journal
                Nanomedicine
                Nanomedicine
                Future Medicine Ltd
                1743-5889
                1748-6963
                March 2019
                March 2019
                : 14
                : 6
                : 753-765
                Affiliations
                [1 ]Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
                [2 ]PharmaExceed srl, 27100 Pavia, Italy
                [3 ]SUPSI, Department of Innovative Technologies, University of Applied Sciences & Arts of Southern Switzerland, Via Pobiette 11, 6928 Manno, Switzerland
                [4 ]Department of Clinical, Surgical, Diagnostic & Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
                [5 ]Fondazione IRCCS Policlinico S. Matteo, Immunology & Transplantation Laboratory/Pediatric Surgery, Cell Factory & Regenerative Medicine Research Center, 27100 Pavia, Italy
                Article
                10.2217/nnm-2018-0240
                © 2019

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