Luciferase Reporter Cell Line - MSC

Combining the powerful capabilities of magnetic guidance with the inherent bioactivity of stem cells-transformed into biohybrid microrobots-holds immense promise for the treatment of various diseases, including cancer. In this study, researchers demonstrated that human mesenchymal stem cells (MSCs) can readily incorporate magnetic particles, and that the resulting biohybrid microrobots can be maneuvered under the guidance of a rotating magnetic field. Such rotating magnetic fields show potential for clinical application in the human body, enabling the precise delivery of therapeutic stem cells to specific target sites within the organism. The researchers confirmed that the process of loading magnetic particles into the stem cells does not adversely affect their biological activity. In investigating this matter, they focused specifically on the expression and functional efficacy of therapeutic genes within the biohybrid microrobots constructed from human MSCs. The results indicated that the incorporation of magnetic particles neither compromised the viability of the human MSCs nor induced apoptosis; furthermore, it did not interfere with the expression of therapeutic genes within the cells. Moreover, the therapeutic effects mediated by the gene products remained unimpaired, and the cells themselves retained their intrinsic migratory capabilities.

Here, researchers collected the cell supernatants from genetically modified MSCs and their corresponding biohybrid microrobots (BHM-MSCs), and applied them to MDA-MB-231 breast cancer cells. A live/dead cell assay revealed that the supernatants from untransduced MSCs, MSC.Luc, and BHM-MSC.Luc did not induce cell death in MDA-MB-231 cells; in contrast, the supernatant from MSC.sTRAIL exerted a significant cytotoxic effect (Figure 1b). In terms of their activity in inducing cell death, MSC.sTRAIL and BHM-MSC.sTRAIL demonstrated comparable levels (Figure 1b). Quantitative analysis of cell mortality indicated that approximately 80% of the MDA-MB-231 cells died following exposure to the supernatants of MSC.sTRAIL and BHM-MSC.sTRAIL, respectively (Figure 1c). Subsequently, the researchers further corroborated these cell death results using a more specific apoptosis assay. DNA hypodiploidy analysis revealed that both MSC.sTRAIL and BHM-MSC.sTRAIL induced apoptosis in 45% to 50% of the MDA-MB-231 cells (Figure 1d). Similar results were obtained when experiments were conducted using a third independent assay at lower sTRAIL concentrations. In this crystal violet-based cell viability assay, the researchers observed a significant decline in cell viability at sTRAIL concentrations as low as 0.01 ng/ml; notably, the loading of microparticles (MPs) had no discernible impact on this activity (Figure 1e). Furthermore, the apoptosis-inducing effects of BHM-MSC.sTRAIL were further validated in two other distinct cancer cell lines.

Figure 1. The sTRAIL secreted by BHM-MSCs is functional. (Gundersen R A, et al., 2023)