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      Mechanoresponsive musculoskeletal tissue differentiation of adipose-derived stem cells

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          Musculoskeletal tissues are constantly under mechanical strains within their microenvironment. Yet, little is understood about the effect of in vivo mechanical milieu strains on cell development and function. Thus, this review article outlines the in vivo mechanical environment of bone, muscle, cartilage, tendon, and ligaments, and tabulates the mechanical strain and stress in these tissues during physiological condition, vigorous, and moderate activities. This review article further discusses the principles of mechanical loading platforms to create physiologically relevant mechanical milieu in vitro for musculoskeletal tissue regeneration. A special emphasis is placed on adipose-derived stem cells (ADSCs) as an emerging valuable tool for regenerative musculoskeletal tissue engineering, as they are easily isolated, expanded, and able to differentiate into any musculoskeletal tissue. Finally, it highlights the current state-of-the art in ADSCs-guided musculoskeletal tissue regeneration under mechanical loading.

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          Most cited references 139

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          Detailed descriptions of the structural features of bone abound in the literature; however, the mechanical properties of bone, in particular those at the micro- and nano-structural level, remain poorly understood. This paper surveys the mechanical data that are available, with an emphasis on the relationship between the complex hierarchical structure of bone and its mechanical properties. Attempts to predict the mechanical properties of bone by applying composite rule of mixtures formulae have been only moderately successful, making it clear that an accurate model should include the molecular interactions or physical mechanisms involved in transfer of load across the bone material subunits. Models of this sort cannot be constructed before more information is available about the interactions between the various organic and inorganic components. Therefore, further investigations of mechanical properties at the 'materials level', in addition to the studies at the 'structural level' are needed to fill the gap in our present knowledge and to achieve a complete understanding of the mechanical properties of bone.
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            Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease.

            Mesenchymal stem cells (MSCs) are a prototypical adult stem cell with capacity for self-renewal and differentiation with a broad tissue distribution. Initially described in bone marrow, MSCs have the capacity to differentiate into mesoderm- and nonmesoderm-derived tissues. The endogenous role for MSCs is maintenance of stem cell niches (classically the hematopoietic), and as such, MSCs participate in organ homeostasis, wound healing, and successful aging. From a therapeutic perspective, and facilitated by the ease of preparation and immunologic privilege, MSCs are emerging as an extremely promising therapeutic agent for tissue regeneration. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSCs to engraft and differentiate into cardiomyocytes and vasculature cells, recruit endogenous cardiac stem cells, and secrete a wide array of paracrine factors. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. This article reviews the current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of MSC therapy for cardiac disease.
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              Embryonic stem cell differentiation: emergence of a new era in biology and medicine.

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              The discovery of mouse embryonic stem (ES) cells >20 years ago represented a major advance in biology and experimental medicine, as it enabled the routine manipulation of the mouse genome. Along with the capacity to induce genetic modifications, ES cells provided the basis for establishing an in vitro model of early mammalian development and represented a putative new source of differentiated cell types for cell replacement therapy. While ES cells have been used extensively for creating mouse mutants for more than a decade, their application as a model for developmental biology has been limited and their use in cell replacement therapy remains a goal for many in the field. Recent advances in our understanding of ES cell differentiation, detailed in this review, have provided new insights essential for establishing ES cell-based developmental models and for the generation of clinically relevant populations for cell therapy.

                Author and article information

                001 419 530 8257 ,
                Biomed Eng Online
                Biomed Eng Online
                BioMedical Engineering OnLine
                BioMed Central (London )
                22 April 2016
                22 April 2016
                : 15
                [ ]Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 USA
                [ ]Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614 USA
                © Trumbull et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

                Funded by: deArce-Koch Memorial Endowment Fund in Support of Medical Research and Development
                Funded by: Office of Undergraduate Research at University of Toledo
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