Endogenous Repair and Regeneration of Injured Articular Cartilage: A Challenging but Promising Therapeutic Strategy

Abstract

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 approachassociated 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.

Strategies for Articular Cartilage Repair and Regeneration

“…In case of AC, the repair procedures after cartilage injury may lead to excessive secretion and deposition of ECM proteins, which may result in fibrocartilage formation (Pearle et al, 2005;Chan et al, 2018). In addition, the inadequate number of stem cells and progenitor cells recruited to the injured site after cartilage damage or microfracture surgery can exacerbate the formation of fibrocartilage (Im, 2016;Hu et al, 2021). The fundamental objective for treating cartilage injury remains the regeneration of hyaline cartilage, or transplant mature hyaline cartilage tissue.…”

Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ

“…However, the lack of MSCs sources and the decreased potential of stem cell culture in vitro restrict its further application [ 9 , 19 ]. Therefore, more studies have focused on improving the in situ regeneration of AC based on endogenous MSCs to overcome the above limitations [ 17 , 18 ]. In particular, joint-resident MSCs are the driving factor for in situ regeneration of AC, among which SMSCs play a dominant role in adult cartilage repair due to their good chondrogenic potential and proximity to AC [ 19 ].…”

“…Then, we applied a rabbit articular cartilage defect model to explore the effect of tFNAs on the migration of SMSCs in vivo. In fact, when cartilage is injured, some chemokines are produced in the articular cavity to promote the migration of MSCs to the injured site [ 18 ]. However, due to insufficient signals, the number of migrating MSCs is usually limited, which leads to difficulty in cartilage regeneration [ 17 ].…”

“…To solve these problems, scientists have recently focused on the in situ regeneration of AC based on endogenous MSCs [ 17 , 18 ]. Some studies have shown that the migration of native joint-resident MSCs is essential for chondrogenesis during embryogenesis, and SMSCs may be the main driver of cartilage repair in adults [ 19 ].…”

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

“…Degradation of articular cartilage is the central pathology of OA, and articular chondrocytes are the main resident cell type in hyaline cartilage, although emerging data indicate that chondroprogenitor cells may also exist. This is why articular chondrocytes are extensively studied ( Vinod et al, 2018 ; Zhang et al, 2019 ; Carluccio et al, 2020 ; Hu et al, 2021 ). Chondrocytes produce extracellular matrix (ECM), mainly type II collagen (Col-II) and proteoglycan including aggrecan ( McCulloch et al, 2017 ).…”