Genetically Modified Mesenchymal Stromal Cells in Cartilage Regeneration

Articular cartilage injury is common in various conditions, including osteoarthritis, rheumatic diseases, and trauma. Current treatments for cartilage injury fail to completely regenerate the damaged cartilage. Mesenchymal stromal cells (MSCs) have emerged as potential candidates for cartilage regeneration. However, MSCs exhibit hypertrophic differentiation, and their chondrogenic ability is reduced in an inflammatory environment. In recent years, genetic modification has been proposed for optimizing MSC-based therapies, some of which are expected to enter clinical trials. This review summarizes recent research findings and developments in genetic engineering strategies to enhance stem cell-based therapy for cartilage regeneration. We also discuss the mechanisms of biofunctions of MSCs in cartilage regeneration and outline the efficacy and safety of the different genetic modification strategies, including viral and nonviral delivery transduction. Finally, we highlight the major challenges and prospects for clinical translation of genetically modified MSCs.

Automated summary

Articular cartilage injury is a common problem in different conditions, but current treatments are not able to fully regenerate damaged cartilage. Mesenchymal stromal cells (MSCs) have potential for cartilage regeneration, but they face challenges such as hypertrophic differentiation and reduced chondrogenic ability in an inflammatory environment. Genetic engineering strategies have been proposed to enhance stem cell-based therapy, and this review summarizes recent research on this topic. The efficacy and safety of different genetic modification strategies, including viral and nonviral delivery transduction, are discussed, as well as the challenges and prospects for clinical translation of genetically modified MSCs.