Abstract
Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.