Bone marrow is a rich source of various stem cells, collectively referred to as bone marrow-derived mesenchymal stem cells (BMSCs). Extensive research has been conducted on these cells in both animal and human studies, revealing their remarkable ability to differentiate into multiple cell types derived from the mesoderm, such as chondrocytes, osteoblasts, and adipocytes, both in vitro and in vivo. As a key player in tissue engineering, BMSCs are currently one of the most promising seed cells due to several advantages. Their isolation and handling are relatively simple, causing minimal damage to the donor. Once harvested, the body can naturally replenish the lost cells, allowing for repeated collection. The culture techniques are well-established, making them easy to apply in clinical settings. Moreover, in vitro induction methods are mature, enabling predictable outcomes. These features make BMSCs an ideal candidate for regenerative medicine.
Using minimally invasive techniques, a small number of BMSCs can be collected, expanded in culture, and then used to generate new tissues, leading to non-invasive or minimally invasive healing. Research on BMSCs has progressed significantly globally, with numerous studies reporting successful differentiation into chondrocytes, osteoblasts, and fat cells, which have been applied in tissue repair and even early clinical trials. Several factors have been identified that promote chondrogenic differentiation, including TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-6, BMP-9, IGF-1, CDMP-1, CDMP-2, and dexamethasone. TGF-β plays a crucial role in the early stages by activating the Smad pathway, which enhances the expression of type II collagen. BMPs, particularly BMP-2 and BMP-6, increase aggrecan production, while IGF-1 amplifies the effects of other growth factors, maintaining the cartilage phenotype. CDMP promotes early chondrogenesis, and dexamethasone acts as a multi-functional inducer, supporting differentiation into multiple lineages.
In addition, environmental factors such as low oxygen levels, low serum concentrations, and high-density cultures also contribute to chondrogenic induction. However, most studies remain limited to in vitro models, with fewer in vivo experiments conducted outside the joint. Studies have shown that after TGF-β1 and dexamethasone treatment, BMSCs can produce large amounts of chondrocyte-specific extracellular matrix components. When mixed with pluronic and injected into nude mice or pigs, they form vascularized fibrous tissue rather than mature cartilage. However, when introduced into the joint environment, they can successfully regenerate cartilage and repair full-thickness defects, suggesting that the intra-articular microenvironment is critical for proper differentiation.
While the exact mechanisms of chondrogenic differentiation are not fully understood, researchers have developed reliable methods to induce this process, increasing the potential for future clinical applications. In addition to chondrogenesis, BMSCs also exhibit strong osteogenic potential. When cultured in media supplemented with β-glycerophosphate, dexamethasone, and vitamin D3, BMSCs gradually acquire an osteoblastic phenotype, forming calcium nodules and expressing markers like alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein. This makes BMSCs a versatile cell source for repairing both cartilage and bone defects.
Articular cartilage defects pose a major challenge in trauma treatment, often leading to joint dysfunction and disability. Traditional methods, such as autologous chondrocyte implantation, frequently result in fibrocartilage formation, which degrades over time. BMSCs, with their dual potential to differentiate into both cartilage and bone, offer a promising alternative. In experimental models, BMSCs were expanded in vitro, induced into cartilage, and combined with scaffolds to repair large articular defects. The results showed superior repair quality compared to traditional methods, demonstrating the feasibility of using BMSCs for tissue-engineered cartilage and bone regeneration.
In clinical settings, BMSCs have also been explored for treating skull and bone defects. Conventional treatments, such as autologous or allogeneic bone grafting, are associated with donor site morbidity and limited availability. By combining BMSCs with biodegradable scaffolds, researchers have successfully repaired large bone defects in patients. Follow-up studies have shown stable integration of the engineered bone with native tissue, without signs of resorption. These findings highlight the potential of BMSC-based tissue engineering to revolutionize the treatment of complex bone and cartilage injuries.
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