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      Mesenchymal Stromal/Stem Cells in Regenerative Medicine and Tissue Engineering

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          Abstract

          As a result of over five decades of investigation, mesenchymal stromal/stem cells (MSCs) have emerged as a versatile and frequently utilized cell source in the fields of regenerative medicine and tissue engineering. In this review, we summarize the history of MSC research from the initial discovery of their multipotency to the more recent recognition of their perivascular identity in vivo and their extraordinary capacity for immunomodulation and angiogenic signaling. As well, we discuss long-standing questions regarding their developmental origins and their capacity for differentiation toward a range of cell lineages. We also highlight important considerations and potential risks involved with their isolation, ex vivo expansion, and clinical use. Overall, this review aims to serve as an overview of the breadth of research that has demonstrated the utility of MSCs in a wide range of clinical contexts and continues to unravel the mechanisms by which these cells exert their therapeutic effects.

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          Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.

          Benedetto Sacchetti, Alessia Funari, Stefano Michienzi … (2007)
          The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.
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            Recent advances in bone tissue engineering scaffolds.

            Susmita Bose, Mangal Roy, Amit Bandyopadhyay (2012)
            Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, made of biodegradable materials that harbor different growth factors, drugs, genes, or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

              Arnold I. Caplan (2007)
              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

                Contributors
                Ross E. B. Fitzsimmons:
                ORCID: http://orcid.org/0000-0002-4856-6252
                Craig A. Simmons:
                ORCID: http://orcid.org/0000-0001-7729-1772
                Journal
                Journal ID (nlm-ta): Stem Cells Int
                Journal ID (iso-abbrev): Stem Cells Int
                Journal ID (publisher-id): SCI
                Title: Stem Cells International
                Publisher: Hindawi
                ISSN (Print): 1687-966X
                ISSN (Electronic): 1687-9678
                Publication date Collection: 2018
                Publication date (Electronic): 19 August 2018
                Volume: 2018
                Electronic Location Identifier: 8031718
                Affiliations
                1Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, Canada M5S 3G9
                2Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, 661 University Ave, Toronto, ON, Canada M5G 1M1
                3Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada T2N 4Z6
                4Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, Canada M5S 3G8
                Author notes

                Academic Editor: Jane Ru Choi

                Author information
                http://orcid.org/0000-0002-4856-6252
                http://orcid.org/0000-0002-3361-7141
                http://orcid.org/0000-0003-4185-1891
                http://orcid.org/0000-0001-7729-1772
                Article
                DOI: 10.1155/2018/8031718
                PMC ID: 6120267
                PubMed ID: 30210552
                SO-VID: 5ba3728b-dd75-4f12-979f-36e07edf804c
                Copyright © Copyright © 2018 Ross E. B. Fitzsimmons et al.
                License:

                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
                Date received : 3 March 2018
                Date revision received : 31 May 2018
                Date accepted : 17 July 2018
                Funding
                Funded by: Canadian Institutes of Health Research
                Award ID: MOP-130481
                Award ID: RMF-111624
                Award ID: MOP-102721
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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