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Address correspondence to: G. Rasul Chaudhry, PhD, Department of Biological Sciences, Oakland University, Rochester, MI 48309, E-mail: [email protected]
Introduction
Cartilage damage resulting from injury or disease is a major public health problem, with degenerative joint disease alone affecting nearly one-third of the adult population in the United States.1,2 Due to the low regenerative and avascular properties of cartilage tissue, current treatment is inefficient, limited by the inability to restore the normal composition and function of damaged cartilage.3,4
Nonoperative treatments can manage pain symptoms by nonsteroidal anti-inflammatory medications and intra-articular injections of corticosteroids or hyaluronic acid, but do little to halt the degeneration process.5 Similarly, surgical procedures, including debridement, microfracture, autograft cartilage transplantation, or full joint replacement, often result in fibrocartilage formation, lacking in the mechanical properties of the native cartilage.6 Use of cartilage autografts is also difficult to practice, due to limited tissue availability and donor site morbidity.2 Autologous transplantation of chondrocytes has been used to reverse the symptoms and pathophysiology of osteoarthritis with limited success.4 More recent approaches have been focused on using a combination of cell therapy and tissue engineering techniques for the regeneration of cartilage tissue.7 Isolated chondrocytes have limited proliferative abilities and have been shown to dedifferentiate during expansion in vitro.8,9
For the above reason, embryonic stem cells (ESCs), with their unlimited ability to self-renew and differentiate into various cell lineages, are an ideal cell source for tissue engineering applications, including cartilage repair and regeneration.10 However, most cell therapies require a high quality population of differentiated derivatives to avoid adverse complications, including teratoma formation. In vivo, ESC fate toward self-renewal or differentiation is controlled by complex interactions of cell-cell and growth factor signaling, organization, and composition of the extracellular matrix (ECM), and the three-dimensional (3-D) biomechanical microenvironment.