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      Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy

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          Abstract

          Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects.

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          Most cited references 168

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          Angiogenesis in life, disease and medicine.

          The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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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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              Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

              Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging.
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                Author and article information

                Journal
                Curr Pharm Des
                Curr. Pharm. Des
                CPD
                Current Pharmaceutical Design
                Bentham Science Publishers
                1381-6128
                1873-4286
                April 2013
                April 2013
                : 19
                : 2459-2473
                Affiliations
                [1 ]Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy;
                [2 ]Laboratorio di Patologia Ortopedica e Rigenerazione Tissutale Osteoarticolare, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy;
                [3 ]Dipartimento di Malattie Cerebrovascolari, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy;
                [4 ]Laboratori Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy;
                [5 ]Dipartimento di Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù, Roma, Italy;
                [6 ]Laboratorio di Terapia Cellulare “Stefano Verri," Dipartimento di Pediatria, Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy;
                [7 ]Laboratorio di Farmacologia delle Cellule Staminali e Medicina Rigenerativa, Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milano, IRCCS Istituto Ortopedico Galeazzi, Italy;
                [8 ]Centro Ricerca M. Tettamanti, Clinica Pediatrica Univ. Milano Bicocca, Monza, Italy;
                [9 ]Divisione di Oncoematologia Pediatrica, Ospedale Infantile Regina Margherita, Torino, Italy;
                [10 ]Laboratorio Centro Trapianti Cellule Staminali e Terapia Cellulare Dipartimento di Scienze Pediatriche e dell'Adolescenza, Università di Torino, Azienda Ospedaliera OIRM-S.Anna, Torino, Italy;
                [11 ]Dipartimento di Scienze Clinico Chirurgiche, Diagnostiche e Pediatriche, University of Pavia, Italy;
                [12 ]Struttura Semplice Terapia Tissutale, Azienda Ospedaliera “Ospedale Niguarda Ca' Granda”, Milan, Italy;
                [13 ]Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy;
                [14 ]Laboratorio Colture Cellulari, Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milan, Italy;
                [15 ]Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Pavia, Italy
                Author notes
                [* ]Address correspondence to this author at the Laboratorio Colture Cellulari, Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy, Tel +39 02 50315072; Fax +39 02 50315093; E-mail: augusto.pessina@ 123456unimi.it
                Article
                CPD-19-2459
                10.2174/1381612811319130015
                3788322
                23278600
                © 2013 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

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