Clinical and experimental approaches to knee cartilage lesion repair and mesenchymal stem cell chondrocyte differentiation

Abstract

Cartilage has poor regeneration capacity due to the scarcity of endogenous stem cells, its low metabolic activity and the avascular environment. Repair strategies vary widely, including microfracture, autologous or allogenic tissue implantation, and in vitro engineered tissues of autologous origin. However, unlike the advances that have been made over more than two decades with more complex organs, including vascular, cardiac or bone tissues, similar advances in tissue engineering for cartilage repair are lacking. Although the inherent characteristics of cartilage tissue, such as the lack of vascularity and low cellular diversity, suggest that it would be one of the more simple tissues to be engineered, its functional weight-bearing role and implant viability and adaptation make this type of repair more complex. Over the last decade several therapeutic approaches and innovative techniques show promise for lasting and functional regeneration of hyaline cartilage. Here we will analyze the main strategies for cartilage regeneration and discuss our experience.

Small animal models to understand pathogenesis of osteoarthritis and use of stem cell in cartilage regeneration

“…69 Onur et al 70 and evaluated histologically and immunohistochemically the scar formation. 75 The scar tissue lacked staining for proteoglycan-rich matrix (SafraninO and ACAN) as well as collagen 1 and 2. These results were consistent with previous reports and indicated that while the microfracture technique is a good system to repair the articular surface, the scar tissue does not present the typical characteristics of hyaline articular cartilage.…”

“…These results were consistent with previous reports and indicated that while the microfracture technique is a good system to repair the articular surface, the scar tissue does not present the typical characteristics of hyaline articular cartilage. 75 A more extensive study on the microfracture model has been recently performed by Matsuoka and colleagues in a mouse model. 76 They analyzed the outcome of this technique on C57Bl/6 mice when surgery was performed at different ages.…”

Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

“…In an inflammatory environment chondrocytes become activated and increase further the expression of proinflammatory cytokines and factors involved in tissue catabolism, namely, matrix metalloproteinases and other proteolytic enzymes, which degrade hyaluronan, aggrecan, collagen, and fibromodulin. Such fragments of matrix components, in turn, also help maintain the production of inflammatory cytokines [ 1 , 14 ]. Alternative therapies for cartilage regeneration in OA should ideally reduce inflammation and promote tissue remodeling.…”

“…Alternative therapies for cartilage regeneration in OA should ideally reduce inflammation and promote tissue remodeling. In this context, the use of mesenchymal stem cells (MSCs) has been pointed out as an interesting therapeutic option [ 14 , 15 ], due to their distinct immunomodulatory, anti-inflammatory, and regenerative properties [ 16 , 17 ]. MSCs anti-inflammatory properties might also be able to change chondrocytes phenotype, decreasing production of inflammatory molecules and favoring the renewal of extracellular components.…”

A versatile, engineered cartilage platform for tissue regeneration and disease modeling

“…Inappropriate management of knee-joint related injuries may lead to serious downstream problems like osteoarthritis (OA), a cartilage degenerative disease that severely affects patient quality-of-life[244]. Currently, a variety of surgical techniques have been developed for treating cartilage-related injuries, including microfracture, mosaicplasty and autologous chondrocyte implantation (ACI)[245].…”