Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration
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Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration OLIVIA S. BEANE1,2 and ERIC M. DARLING1,2,3,4 1 Center for Biomedical Engineering, Brown University, Providence, RI, USA; 2Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI, USA; 3Department of Orthopaedics, Brown University, Providence, RI, USA; and 4School of Engineering, Brown University, Providence, RI, USA
(Received 23 May 2012; accepted 8 August 2012; published online 21 August 2012) Associate Editor Michael S. Detamore oversaw the review of this article.
applications (Fig. 1). The motivation for exploring the regenerative potential of these cells results from the lack of effective therapies currently available for patients suffering from joint diseases. One example is osteoarthritis, a pathology characterized by the degradation of hyaline cartilage.79 Aside from total joint replacement, possible forms of treatment include microfracture, which allows for subchondral MSCs to populate the defect, and autologous chondrocyte implantation, which is a treatment using ex vivo expanded chondrocytes and, potentially, stem cells. Unfortunately, both procedures can result in the formation of fibrocartilage, a mechanically inferior tissue to healthy hyaline cartilage. Tissue engineering approaches using primary chondrocytes are non-ideal since undamaged cartilage has to be destroyed to obtain the cells, and in vitro expansion is necessary to achieve sufficient cell numbers. This process also takes precious weeks, results in dedifferentiation, and raises the risk of contamination. Stem cells have become an attractive therapeutic alternative due to their relative abundance and multipotent capabilities, specifically their ability to undergo chondrogenesis.148 An ideal stem cell source has yet to be identified, as each has strengths and weaknesses. Studies have characterized these populations extensively, highlighting large variations in the different cell types, such as ease of isolation, differentiation potential, and surface marker expressions. Additional research has led to progress within all stem cell fields to optimize growth factor cocktails and delivery systems, although to varying degrees of success. To induce stem cell chondrogenesis, many in vitro strategies have been explored, including mechanical stimulation, the use of scaffolds or growth factors, or a combination of these techniques.110 The most
Abstract—The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic
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