Human and mouse meniscus progenitor cells and their role in meniscus tissue regeneration

Abstract

Osteoarthritis (OA) is a degenerative disease of hyaline cartilage. The cartilage is an avascular tissue, once damaged it is difficult to repair. Articular cartilage is responsible for the smooth, frictionless, and painless moment of the knee joint. Severe loss or complete destruction of the articular cartilage results in highly frictional and painful moment of the knee joint, as is often the case in the late stages of OA. Total joint replacement remains the ultimate solution. However, there are many other options emerging to repair or regenerate the cartilage using various types of stem cells, but they might lead to some serious consequences. For example, transplantation of embryonic stem cells may result in teratoma formation. Applications of induced pluripotent stem cells are associated with possible viral integration. Alternatively, the concept of progenitor or repair cells in situ arises, and, for example, migratory chondrogenic progenitor cells (CPCs) were found in the later stages of human osteoarthritic cartilage in vivo. They have a tremendous ability for cartilage repair with no serious risk factors known so far. However, CPCs still face some challenges, for example, how to provoke them in situ to repair the tissue in a physiological manner. Secondly, CPCs have a limited life span at least in vitro. Furthermore, so far, there is no single optimized method available to achieve a complete chondrogenic differentiation of stem cells. More recently, a tiny organelle of the cells, known as primary cilium might be found to be instrumental for stem cell differentiation. This ‘physical projection’ of the cell acts like an antenna, and is considered as dual sensor of mechanochemical signals. This sensor has also been found on CPCs and their numbers have been shown to be reduced on chondrocytes derived from the temporomandibular joint (TMJ) of the discoidin domain receptor 1 knockout (DDR-1 KO) mouse. OA is not only restricted to large joints but also affects small joints like the TMJ. It is well known that chondrocytes in the articular cartilage do not make direct cell-to-cell contacts, instead they rely on cell-matrix-interactions via cell receptors, for example, integrins or DDRs for their communication. DDR-1 KO mice exhibit typical symptoms of OA of the TMJ cartilage. The chondrocytes derived from the TMJ cartilage of DDR-1 KO mice maintained their osteoarthritic characteristics such as a high expression of runx2 and collagen type I as typical osteogenic signature, and a low expression of sox9, collagen type II and aggrecan known to be relevant for the chondrogenic differentiation. The osteoarthritic characteristic could be reversed to a more normal chondrocyte type via the knockdown of runx2 or exposure of these cells to a three-dimensional environment in the presence of extracellular matrix (ECM) components such as laminins and nidogen. Their reversal towards the chondrogenic phenotype would also be of great importance in the pathogenesis of meniscus degeneration. Meniscus most often is the starting point for the development of OA of the knee joint. The meniscus is a fibrocartilaginous tissue, which acts as shock absorber. Furthermore, meniscus damaging makes the whole scenario of OA pathogenesis worse, by enhancing the cartilage degradation. The inner part of the meniscus is avascular in nature and therefore, once damaged it has a very limited self-repair capacity. However, there are other options available like the partial removal of the meniscus, which results in a short-term relief, but cannot prevent the long-term consequences, which ultimately lead to the development of OA. The inner part of the human meniscus harbors unique meniscus progenitor cells (MPCs) and can be directed towards meniscus regeneration via the TGFβ signaling pathway. Additionally, mouse meniscus progenitor cells (MMPCs) were investigated in healthy (wild type) meniscus tissue. These cells were traced ex vivo using immuno-histochemical techniques. They also maintained their stem cell characteristics in vitro as well, as shown via their stem cell marker expression and their mulitipotency. Many critical consequences are associated with the application of various stem cells for cartilage regeneration as a therapy. Here, I concentrated on tissue specific cells, progenitor cells in situ, already present in diseased cartilage. These cells are well determined towards chondrogenic differentiation and might only need minor manipulations to fulfill their final determination to produce native-like hyaline cartilage.