Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

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.

Comparison of Biological Features of Wild European Rabbit Mesenchymal Stem Cells Derived from Different Tissues

“…Rabbit MSCs (rMSC) have been widely used as preclinical models for orthopedic problems, specifically bone, articular cartilage, cartilage cell therapy, ligament reconstruction, and spinal fusion, as well as for cardiovascular regenerative medicine strategies [ 25 , 26 , 27 , 28 , 29 ]. Although rMSCs are being investigated in these models, they have not been fully characterized in terms of immunophenotype and differentiation potential, and many tissues have not yet been explored as a source of MSC in the rabbit.…”

Extracellular Vesicles Released from Stem Cells as a New Therapeutic Strategy for Primary and Secondary Glomerulonephritis

“…Of interest, their differentiation can be also conditioned and improved with specific cues to make them more suitable for therapeutic applications. For example, cultivating MSC in media with a combination of different glycosaminoglycans can stimulate commitment of SCs to chondrocyte progenitors and promote differentiation towards mature chondrocytes [ 35 ]. In general, MSCs are more pluripotent than normal somatic cells but, unlike embryonic cells, they do not indefinitely self-renew [ 36 ].…”

Targeted treatment for osteoarthritis: drugs and delivery system

“…Chondroitin sulfate (CS) is a sulfated GAG and an important component of the cartilage extracellular matrix (Alessio et al., 2021 ). It is widely used in the adjuvant therapy of OA due to its anti-inflammatory, anti-oxidative and anti-apoptotic effects (Henrotin et al., 2010 ).…”