Comparison of multiple synthetic chondroinductive factors in pellet culture against a TGF-β positive control

by Selleckchem | Aug 25 2023

Despite the advances in surgical and cell therapy regenerative techniques for cartilage repair, the challenge is to overcome an inferior fibrocartilage repair tissue. In vitro, TGF-β1 and TGF-β3 are the primary growth factors employed to induce chondrogenic differentiation. However, the clinical application of native proteins may present challenges regarding stability, cost, or reproducibility. Therefore, there remains an unmet clinical need for the identification of small chondroinductive synthetic molecules. From the literature, two peptides-CM10 and CK2.1-appear to be promising candidates; however, they have not been directly compared to TGF-β with human bone marrow-derived stem cells (hBMSCs). Similarly, two promising compounds-kartogenin and SM04690-have been reported in the literature to exhibit chondroinductive potential in vivo and in vitro; however, kartogenin was not directly compared against TGF-β. In the current study, we evaluated the chondroinductive potential of CM10, CK2.1, kartogenin, and SM04690, and directly compared them to each other and to a TGF-β3 positive control. Following 21 days of culture, none of the evaluated chondrogenic factors, either individually or even in combinations of two, resulted in a higher gene expression of chondrogenic markers as compared to TGF-β3. Additionally, no collagen II gene expression was detected except in the TGF-β3 positive control group. Given that the evaluated factors have confirmed efficacy in the literature, but not in the current study with a positive control, there may be value in the future identification of new chondroinductive factors that are less situation-dependent, with rigorous evaluations of their effect on chondrogenesis using positive controls.

Comments:

The passage highlights the challenge of achieving superior cartilage repair tissue using current surgical and cell therapy regenerative techniques. While TGF-β1 and TGF-β3 have been commonly used to induce chondrogenic differentiation in vitro, their clinical application may face limitations such as stability, cost, and reproducibility. Therefore, there is a need to identify small synthetic molecules that can promote chondroinduction. The literature suggests that CM10 and CK2.1 peptides, as well as kartogenin and SM04690 compounds, hold promise as potential chondroinductive agents. However, direct comparisons with TGF-β and evaluation using human bone marrow-derived stem cells (hBMSCs) have been lacking.

In the current study, the chondroinductive potential of CM10, CK2.1, kartogenin, and SM04690 was assessed and compared to each other and to a TGF-β3 positive control. After a 21-day culture period, none of the evaluated factors, individually or in combinations, resulted in higher gene expression of chondrogenic markers compared to TGF-β3. Furthermore, only the TGF-β3 positive control group showed collagen II gene expression. This finding indicates that, despite the reported efficacy of the evaluated factors in the literature, they did not surpass the chondroinductive potential of TGF-β3 in this study, which used a positive control.

Based on these results, it is suggested that future research should focus on identifying new chondroinductive factors that are less dependent on specific situations and should include rigorous evaluations of their effect on chondrogenesis using positive controls. This approach would provide a more comprehensive understanding of the potential of new chondroinductive agents and their ability to outperform established growth factors like TGF-β3.