Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research

Liposarcoma is one of the most common soft tissue sarcomas, however, its occurrence rate is still rare compared to other cancers. Due to its rarity, in vitro experiments are an essential approach to elucidate liposarcoma pathobiology. Conventional cell culture-based research (2D cell culture) is still playing a pivotal role, while several shortcomings have been recently under discussion. In vivo, mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell culture. However, they do not fully recapitulate human dedifferentiated liposarcoma (DDLPS) characteristics. Therefore, three-dimensional (3D) culture systems have been the recent research focus in the cell biology fi eld with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fi ll in the gap between them. Given the liposarcoma rarity, we believe that 3D cell culture techniques, including 3D cell cultures/co-cultures, and Patient-Derived tumor Organoids (PDOs), represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy development. In this review, we fi rst provide a general overview of 3D cell cultures compared to 2D cell cultures. We then focus on one of the recent 3D cell culture applications, Patient-Derived Organoids (PDOs), summarizing and discussing several PDO methodologies. Finally, we discuss the current and future applications of PDOs to sarcoma, particularly in the fi eld of liposarcoma.