Concise Review: Mesenchymal Stem Cells for Functional Cartilage Tissue Engineering: Taking Cues from Chondrocyte-Based Constructs

Abstract

Osteoarthritis (OA), the most prevalent form of joint disease, afflicts nine percent of the US population over the age of thirty and costs the economy nearly $100 billion annually in healthcare and socioeconomic costs. It is characterized by joint pain and dysfunction, though the pathophysiology remains largely unknown. Due to its avascular nature and limited cellularity, articular cartilage exhibits a poor intrinsic healing response following injury. As such, significant research efforts are aimed at producing engineered cartilage as a cell-based approach for articular cartilage repair. However, the knee joint is mechanically demanding, and during injury, also a milieu of harsh inflammatory agents. The unforgiving mechano-chemical environment requires tissue replacements that are capable of bearing such burdens. The use of mesenchymal stem cells (MSCs) for cartilage tissue engineering has emerged as a promising cell source due to their ease of isolation, capacity to readily expand in culture, and ability to undergo lineage-specific differentiation into chondrocytes. However, to date, very few studies utilizing MSCs have successfully recapitulated the structural and functional properties of native cartilage, exposing the difficult process of uniformly differentiating stem cells into desired cell fates and maintaining the phenotype during in vitro culture and after in vivo implantation. To address these shortcomings, here, we present a concise review on modulating stem cell behavior, tissue development and function using well-developed techniques from chondrocyte-based cartilage tissue engineering.

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[127] However, a cartilage-centric approach may be short sighted and is liable to be unsuccessful in terms of the function of the whole joint unless the global health of all joint tissues are successfully addressed. [127] However, a cartilage-centric approach may be short sighted and is liable to be unsuccessful in terms of the function of the whole joint unless the global health of all joint tissues are successfully addressed.…”

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ‐Caprolactone) Scaffolds

“…Cartilage self‐repair occurring upon injury or degenerative joint disease such as osteoarthritis or rheumatoid arthritis is hampered by the intrinsic avascular nature and low cellularity of this tissue. Appropriate therapeutic strategies to regenerate cartilage with properties similar to the native tissue and with long‐term functionality have yet to be developed . Cartilage tissue engineering (CTE) approaches, aiming at fabricating tissue substitutes that recapitulate the biochemical, structural, and mechanical properties of native cartilage, have been introduced as promising alternatives to current clinical surgical methods .…”

Polymer Fiber Scaffolds for Bone and Cartilage Tissue Engineering

“…The fact that cartilage tissues are relatively avascular and have limited cell migration ability results in a low endogenous healing ability; thus, they cannot automatically repair damage after disease or injury . Once injured, the cartilage tissues lose much of their carrying capacity, making the adjacent cartilage more prone to wear and tear.…”