Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges

Abstract

Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

Three‐dimensional plotted alginate fibers embedded with diclofenac and bone cells coated with chitosan for bone regeneration during inflammation

“…The control, on the other hand, had a much lower cell number on day 10 compared to the normal cell growth when the concentrations of inflammatory compounds were the highest. This indicates that cells in the coated sample were exposed to almost no inflammatory compounds, which have been reported to slow down their proliferation and differentiation . This was most likely due to the chitosan coating, since diclofenac no longer existed in the medium on day 10.…”

Production and evaluation of decellularized extracellular matrix hydrogel for cartilage regeneration derived from knee cartilage

“…Besides, mesenchymal stem cells (MSCs) are capable of differentiating into bone, cartilage, and adipose lineages (Baghaban Eslaminejad & Bordbar, ). Chondrogenic differentiation of MSCs confirmed in various studies, and have also been applied in clinical trials (Borakati, Mafi, Mafi, & Khan, ; Cruz et al, ; Freitag, Shah, Wickham, Boyd, & Tenen, ; Lee & Wang, ). Besides, injectable hydrogels have been implanted in vivo through minimally invasive techniques, providing therapeutic treatments without invasive surgical procedures (Li et al, ; Takei, Sugihara, Yoshida, & Kawakami, ).…”

Stem cell secretome, regeneration, and clinical translation: a narrative review

“…However, risks such as teratoma formation and immune rejection, persist even after proper engraftment of stem cells (15). These limitations have severely handicapped the in vivo use of stem cells for tissue regeneration (16). Fortunately, stem cell conditioned media, or alternatively named secretome and/or exosome, has been described as an effective alternative.…”