APPLICATION OF GENETICALLY MODIFIED INDUCED PLURIPOTENT STEM CELL LINES IN ARTICULAR CARTILAGE TISSUE ENGINEERING

Abstract

The restoration of hyaline cartilage poses a complex clinical and scientific challenge due to its low regenerative potential. Joint cartilage injuries contribute to the development of osteoarthritis and, as a consequence, loss of joint function, and subsequent disability. Surgical approaches such as mosaic chondroplasty and microfracture are applicable only to relatively small defects and are unsuitable for patients with degenerative cartilage conditions. Developing of cell therapies using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising direction for joint cartilage tissue reconstruction. iPSCs have high proliferative activity, allowing the generation of autologous cells in the amount required to restore an individual’s articular defect. The CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables genetic modification of iPSCs to produce progenitor cells with specific characteristics and properties. This review contains scientific studies of highly specialized focus on combining iPSC and CRISPR-Cas technologies for research in cartilage regenerative medicine. We have compiled articles over the past twelve years, since CRISPR-Cas became available to the world community. Currently, for the field of regenerative medicine of articular cartilage CRISPR-Cas is used to increase the effectiveness of chondrogenic differentiation of iPSCs and to obtain a chondroprogenitor population with a high homogeneity. Additionally, deletion of a sequence of pro-inflammatory cytokine receptors is conducted to produce inflammation-resistant tissue. Finally, knockout of major histocompatibility complex components allows the creation of hypoimmunogenic chondrocytes. These approaches contribute to the development of personalized medicine and may, in the long term, lead to improved quality of life for the global population.