Articular cartilage tissue engineering using genetically modified induced pluripotent stem cell lines

Mature hyaline cartilage has a low regenerative potential and its repair remains a complex clinical and research issue. Articular cartilage injuries often contribute to the development of osteoarthritis, resulting in loss of joint function and patient disability. Surgical techniques for repairing articular surfaces, such as mosaic chondroplasty and microfracture, which are designed for small defects, cannot be used for degenerative and dystrophic cartilage lesions. Cell therapy using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising approach to reconstruct articular cartilage tissue. iPSCs have high proliferative activity, which allows the harvesting of autologous cells in quantities necessary to repair a joint defect. CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables the genetic modification of iPSCs to obtain progenitor cells with specific characteristics and properties. This review describes specific research papers on the combined use of iPSC and CRISPR-Cas technologies for the evaluation of cartilage regenerative medicine. Papers were evaluated for the last twelve years since CRISPR-Cas technology was introduced to the global community. CRISPR-Cas is currently being used to address therapeutic issues in articular cartilage regeneration by increasing the efficiency of chondrogenic differentiation of iPSC lines and harvesting a more homogeneous population of chondroprogenitor cells. Another approach is to remove the pro-inflammatory cytokine receptor sequence to produce inflammation-resistant cartilage. Finally, knocking out genes for components of the major histocompatibility complex allows harvesting chondrocytes that are invisible to the recipient's immune system. This kind of research contributes to personalized healthcare and can improve the quality of life of the world's population in the long term.