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Selective removal of undifferentiated iPS cells from mesenchymal stem cells
Mesenchymal stem cells (MSCs) are present in all tissues and are known to directly or indirectly promote tissue regeneration. There are several challenges in acquiring MSCs from living organisms for cell replacement therapies, such as invasiveness, proliferation limitations, and variability in biological properties between different samples.
To avoid these issues, MSC production from iPS cells (iMSCs) represents a non-invasive, robust, and highly reproducible alternative. However, there is a risk of teratoma formation from residual undifferentiated iPS cells when using iMSCs for transplantation therapy. Therefore, a method to remove such unwanted iPS cells before transplantation is crucial for realizing safe iMSC-based cell therapy.
Previous studies have shown that mouse ES/iPS cells can be selectively removed by treatment with DHODH inhibitors, but it was unknown whether the same is true for human cells. This study showed that BRQ treatment selectively removes undifferentiated human iPS cells from iMSCs by activating cell cycle arrest and apoptosis. On the other hand, iMSCs were unaffected by the treatment and maintained their properties and differentiation potentials.
The iMSCs created by Associate Professor Ikeya and his colleagues are produced by a two-step induction method via an intermediate cell type called neural crest cells. Since the process involves extracting neural crest cells and removing undifferentiated cells using a cell sorter, there is little risk of teratoma formation for small-scale studies. However, many more cells may be transplanted for human clinical applications compared to experiments using small animals such as mice, thus increasing the risk of tumorigenesis proportionately.
The findings from this study establish an additional level of safety for using iMSCs in the future for cell therapy and provide patients undergoing iMSC-based treatments with extra peace of mind. The results were published online in Frontiers in Cell and Developmental Biology on February 6, 2023.
More information: Ziadoon Al-Akashi et al, Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification, Frontiers in Cell and Developmental Biology (2023). DOI: 10.3389/fcell.2023.1089945
Provided by Kyoto University