Endogenous repair and regeneration of injured articular cartilage: A challenging but promising therapeutic strategy

Articular cartilage (AC) has a very limited intrinsic repair capacity after injury or disease. Although exogenous cell-based regenerative approaches have obtained acceptable outcomes, they are usually associated with complicated procedures, donor-site morbidities and cell differentiation during ex vivo expansion. In recent years, endogenous regenerative strategy by recruiting resident mesenchymal stem/progenitor cells (MSPCs) into the injured sites, as a promising alternative, has gained considerable attention. It takes full advantage of body's own regenerative potential to repair and regenerate injured tissue while avoiding exogenous regenerative approach-associated limitations. Like most tissues, there are also multiple stem-cell niches in AC and its surrounding tissues. These MSPCs have the potential to migrate into injured sites to produce replacement cells under appropriate stimuli. Traditional microfracture procedure employs the concept of MSPCs recruitment usually fails to regenerate normal hyaline cartilage. The reasons for this failure might be attributed to an inadequate number of recruiting cells and adverse local tissue microenvironment after cartilage injury. A strategy that effectively improves local matrix microenvironment and recruits resident MSPCs may enhance the success of endogenous AC regeneration (EACR). In this review, we focused on the reasons why AC cannot regenerate itself in spite of potential self-repair capacity and summarized the latest developments of the three key components in the field of EACR. In addition, we discussed the challenges facing in the present EACR strategy. This review will provide an increasing understanding of EACR and attract more researchers to participate in this promising research arena.