Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

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.

Adipose-Derived Extract Suppresses IL-1β-Induced Inflammatory Signaling Pathways in Human Chondrocytes and Ameliorates the Cartilage Destruction of Experimental Osteoarthritis in Rats

“…Currently, the potential mechanisms of stem cells in articular cartilage regeneration can be divided into two main categories: the "differentiation theory" and "paracrine theory" [33]. Differentiation theory is an approach to articular cartilage regeneration therapy in which stem cells directly differentiate into chondrocytes.…”

Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential

“…In the injured cartilage tissue, activated chondrocytes increase the production of cartilage, degrading catabolic enzymes, proinflammatory cytokines, and oxidative stress inducers, which induces the degradation of the cartilage matrix and chondrocyte apoptosis or necrosis via activation of the NF-κB pathway, leading to irreversible articular damage and functional impairment [ 149 , 150 ]. Standard surgical clinical techniques cannot regenerate the articular cartilage [ 151 ]. Due to the lack of blood vessels, nerves, and lymphatic vessels and the restriction of the dense extracellular matrix (ECM) on cartilage cells, the post-injury self-healing ability of the articular cartilage is very limited [ 148 , 151 , 152 ].…”

“…Standard surgical clinical techniques cannot regenerate the articular cartilage [ 151 ]. Due to the lack of blood vessels, nerves, and lymphatic vessels and the restriction of the dense extracellular matrix (ECM) on cartilage cells, the post-injury self-healing ability of the articular cartilage is very limited [ 148 , 151 , 152 ]. A new approach in cartilage-injury tissue therapy is regenerative medicine [ 148 , 151 ].…”

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

“…Studies have shown that pretreatment is an effective way to improve the ability of cells to resist adverse microenvironments. Stem cell pretreatment can improve cell survival and differentiation potential, regulate immune response, inhibit fibrosis, and enhance cell secretion of anti-inflammatory factors [ 50 ]. Therefore, a stem cell pretreatment strategy has also received a lot of attention in the field of releasing EVs to treat OA.…”