Abstract Patient derived 3D models of pediatric brain tumors are being utilized in precision medicine for both function studies and PK/PD investigations as they are more physiologically and clinically relevant. The primary ETMR cell line, designated BT183, was originally derived from a treatment naive 2-year-old male patient and has been shown to maintain key genetic and histologic features, including the C19MC amplification and LIN28A overexpression that are required for diagnosis. The ETMR 3D tumorsphere model used to-date contains very few of its characteristic histological feature of multilayered rosettes. We have developed a more clinically relevant 3D model of ETMR through adaptation of the culture media and allowing growth above 700 µm in diameter prior to functional and drug studies. Our pseudo-organoid model contains abundant multilayered rosettes that resemble patient ETMR histology. When compared to the routinely used 3D stem cell model, we show that our models diverge in growth kinetics after they reach ∼500 µm in diameter. The change in growth kinetics after 500 µm is thought to be due to the formation of abundant rosettes and thus different cellular phenotypes compared to the 3D stem cell model. Preliminary studies have detected a difference in drug sensitivity between these two ETMR models but only when they are grown to ∼700 µm in diameter prior to the start of treatment. Ongoing studies are focused on the development of larger multicellular 3D pseudo-organoid models that surpass the size and complexity of what can be achieved in preclinical mouse models.
Maas et al. (Fri,) studied this question.
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