Abstract
Mesenchymal stromal cells (MSCs) are currently used for cartilage cell therapy because of their well proven capacity to differentiate in chondrocytes. The advantage of MSC-based therapy is the possibility of producing a high number of chondrocytes for implants. The transplant procedure, however, has some limitations, since MSCs may produce non-functional chondrocytes. This limit has been challenged by cultivating MSC in media with hydrogels containing hyaluronic acid (HA), extractive chondroitin sulfate (CS), or bio-fermentative unsulphated chondroitin (BC) alone or in combination. Nevertheless, a clear study of the effect of glycosaminoglycans (GAGs) on chondrocyte differentiation is still lacking, especially for the newly obtained unsulfated chondroitin of biotechnological origin. Are these GAGs playing a role in the commitment of stem cells to chondrocyte progenitors and in the differentiation of progenitors to mature chondrocytes? Alternatively, do they have a role only in one of these biological processes? We evaluated the role of HA, CS, and – above all – BC in cell commitment and chondrocyte differentiation of MSCs by supplementing these GAGs in different phases of in vitro cultivation. Our data provided evidence that a combination of HA and CS or of HA and BC supplemented during the terminal in vitro differentiation and not during cell commitment of MSCs improved chondrocytes differentiation without the presence of fibrosis (reduced expression of Type I collagen). This result suggests that a careful evaluation of extracellular cues for chondrocyte differentiation is fundamental to obtaining a proper maturation process.
Highlights
Our joints are endowed with articular cartilage to tolerate daily physical and mechanical stress
The stemness, cell commitment and differentiation of mesenchymal stromal cells (MSC) are regulated by extracellular matrix (ECM) and physical and chemical cues
MSCs were cultivated in a proliferating medium (PM) and this was exchanged for a differentiating medium (DM) containing signaling molecules known to induce chondrocyte lineage selection and differentiation (Solchaga et al, 2011)
Summary
Our joints are endowed with articular cartilage to tolerate daily physical and mechanical stress. The homeostasis and tissue repair of cartilage is inefficient due to the lack of blood vessels and the sparse, isolated chondrocytes This condition renders cartilage prone to degeneration due to the onset of diseases, such as osteoarthritis (OA), a disabling and painful pathology, which affects a great number of individuals in their 50s and beyond (Dulay et al, 2015). This disease results from progressive degradation of cartilage with loss of Type II collagen and of GAGs, such as hyaluronic acid (HA) and chondroitin sulfate (CS) (Dulay et al, 2015; Fonsi et al, 2020). The intra-articular injection of mixtures containing either HA or CS or HA + CS have already been used or are in clinical trial evaluation (Pederzini et al, 2013; Kloppenburg, 2014; Rivera et al, 2016)
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