Cartilage replacement at joints represents a tremendous challenge for regenerative medicine. While growing cartilage in culture is possible, scaling this technology up to generate enough high-quality articular cartilage (the kind of cartilage found at joints), is still a distinct challenge. To date, stem cell treatments can heal small breaches in cartilage, but reconstructing large lesions is still not possible. In general, cartilage at joints has very poor healing properties, and therefore, is a major challenge in orthopedics.
A major improvement in therapeutics is the use of a technique called “autologous chondrocyte implantation” or ACI. ACI involves the delivery of healthy cartilage-making cells (chondrocytes) from the patient’s own body after these cells have been grown and expanded in culture. In order to coax these cartilage-making cells to make cartilage, special scaffolds are used that provide a three-dimensional matrix upon which the chrondrocytes grow and form cartilage. These 3-D scaffolds are essential to keep the chondrocytes differentiated and making cartilage.
One of the most promising types of scaffolds for making cartilage are “bioactive 3D scaffolds.” These types of scaffolds can deliver growth factors and other molecules to the chrondrocytes and boost their growth and cartilage production.
In a recent publication, Andrei Moroz and colleagues in the Extracellular Matrix Laboratory at the Botucatu Institute of Biosciences, São Paulo State University, Brazil, have used mesenchymal stem cells (MSCs) from rabbit bone marrow and differentiated them into chondrocytes. This allowed them to use stem cells from bone marrow instead of harvesting cartilage from the joints, which can be very painful and deleterious to the joint. The main innovation in this paper was the use of a platelet-lysate-based 3D bioactive scaffold to support the chondrogenic differentiation and maintenance of MSCs.
MSCs from adult rabbit bone marrow were isolated, characterized, and grown in 60 microliters of platelet lysate from rabbit blood. Platelets are very small cells from circulating blood that assist in the formation of clots that staunch bleeding after a blood vessel in damaged. Platelets are easy to isolate from circulating blood and the rabbit platelet-lysate clot scaffold was maintained is a standard tissue culture medium (Dulbecco’s Modified Eagle Medium Nutrient Mixture F-12) that was supplemented with other molecules known to induce cartilage formation in MSCs. After three weeks in culture, the MSCs were examined in detail. Not only were they nice and round, but they were filled with cartilage-specific molecules, and clumped together like chondrocytes.
According to this research group, they are on to something with this platelet-lysate bioactive scaffold. It provided a suitable system for culturing MSCs and allowed them to make lots of cartilage. The scaffold also was easy to make, and maintained the MSCs in a cartilage-making state without causing cell death or stressing the cells. Therefore, it might provide an alternative to autologous chondrocyte implantation. The next steps in this research will be to use this engineered cartilage to repair damaged joints to see if the cartilage made by cells embedded in platelet-lysate 3D bioactive scaffolds can act as functional cartilage.