Use of human induced pluripotent stem cells for cartilage regeneration in vitro and within chondral defect models of knee joint cartilage in vivo: a Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic literature review

Articular cartilage has limited regenerative ability when damaged through trauma or disease. Failure to treat focal chondral lesions results in changes that inevitably progress to osteoarthritis. Osteoarthritis is a major contributor to disability globally, which results in significant medical costs and lost wages every year. Human induced pluripotent stem cells (hiPSCs) have long been considered a potential autologous therapeutic option for the treatment of focal chondral lesions. Although there are significant advantages to hiPSCs over other stem cell options, such as mesenchymal and embryonic stem cells, there are concerns regarding their ability to form bona fide cartilage and their tumorgenicity in vivo.The authors carried out a systematic literature review on the use of hiPSCs to produce differentiated progeny capable of producing high-quality cartilage in vitro and regenerate cartilage in osteochondral defects in vivo in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight studies were included in the review that used hiPSCs or their derived progeny in xenogeneic transplants in animal models to regenerate cartilage in osteochondral defects of the knee joint. The in vitro-differentiated, hiPSC-derived and in vivo defect repair ability of the hiPSC-derived progeny transplants were assessed.Most studies reported the generation of high-quality cartilage-producing progeny that were able to successfully repair cartilage defects in vivo. No tumorigenicity was observed.The authors conclude that hiPSCs offer a valuable source of cartilage-producing progeny that show promise as an effective cell-based therapy in treating focal chondral lesions.