Well Structured Cartilage Grown from Embryonic Stem Cells

Tissue engineering of new cartilage is an important goal in the field of regenerative medicine, but it has proven challenging to obtain the necessary structural properties. Natural cartilage is a resilient, strong tissue. Incremental progress towards this goal has been made over the years, as researchers explored the space of the possible. Now we see demonstrations such as the one noted here, in which sizable sections of engineered cartilage can be produced from embryonic stem cells, and the tissue exhibits the desired structural properties. If this can be achieved with embryonic stem cells, then it can in principle also be achieved with induced pluripotent stem cells, either generated from a patient cell sample, or made universal by knocking out MHC class I and II receptors and other immune-related signals in order to be used in any patient without rejection.

Articular cartilage functions as a shock absorber and facilitates the free movement of joints. Currently, there are no therapeutic drugs that promote the healing of damaged articular cartilage. Limitations associated with the two clinically relevant cell populations, human articular chondrocytes and mesenchymal stem cells, necessitate finding an alternative cell source for cartilage repair. Human embryonic stem cells (hESCs) provide a readily accessible population of self-renewing, pluripotent cells with perceived immunoprivileged properties for cartilage generation.

We have developed a robust method to generate 3D, scaffold-free, hyaline cartilage tissue constructs from hESCs that are composed of numerous chondrocytes in lacunae, embedded in an extracellular matrix containing Type II collagen, sulphated glycosaminoglycans and Aggrecan. The elastic (Young's) modulus of the hESC-derived cartilage tissue constructs (0.91 ± 0.08 MPa) was comparable to full-thickness human articular cartilage (0.87 ± 0.09 MPa). Moreover, we have successfully scaled up the size of the scaffold-free, 3D hESC-derived cartilage tissue constructs to between 4.5 mm and 6 mm, thus enhancing their suitability for clinical application.

Link: https://doi.org/10.1038/s41598-021-97934-9

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