![]() ![]() It indicated that the 2D cell culture model could be an inaccurate model for drug development. The clear evidence was the experiments using the immortalized tumor cell lines grown in the 2D culture systems resulted a 95% drug response failure rate in human subjects. However, the in vivo environment provides cell-cell and cell-extracellular matrix (ECM) interactions in a 3D structure, and the 2D monolayer cells might not accurately mimic the actual 3D environment of the in vivo cells. At the very beginning of the cell culture era, the cultures were mostly carried out under an adherent condition, which is called the 2D monolayer cell culture model. The selection of cell culture procedures for cancer research is the key for the better understanding of tumor biology, resulting in the optimal and effective conditions for radio/chemotherapy as well as the discovery of new cancer treatment strategies. Since then, the technique has been continuously improved, and cell-based experiments can be effortlessly conducted based on such cell culture technique due to cell banking. In 1907, Harrison et al implemented the cell culture technique to his research, exploring the origin and the development of nerve fibers. In addition, we also present the possibility to be applied in cancer and stem cell aspects. Here, we aim to demonstrate the necessity of novel 3D cell culture systems and describe, compare, and contrast the 3D cell cultures techniques that has been developed to date. Thus, the study of cellular phenomena in a conditions that closely imitates in vivo scenery could be elaborately constructed in vitro. Over the last decade, a variety of in vitro platforms was developed to achieve the 3D culture systems for cancer and stem cell applications such as novel drug development, cancer and stem cell biological research, tissue engineering for in vivo implantation, and other experimental cell analyses. The 3D cell culture systems provided the novel cell-based assays with more physiological relevance, especially the behavioral similarity to the in vivo cells. Such concerns inspired the emergence of 3D cell cultures systems, a promising approach to overcome the inconsistency between cell-based assays and clinical trials. As a consequence, there are many different features that 2D‑cultured cells possess compared with in vivo cells such as morphological characteristics, proliferation and differentiation potentials, interactions of cell-cell and cell-surrounding matrix, and signal transduction. The key limitation of traditional 2D culture is the failure to imitate the in vivo architecture and microenvironments. One possible cause of the failure is that drug responses of 2D cell cultures systems did not consistently predict the outcome of clinical studies. ![]() Less than 5% of anticancer agents and small molecule oncology therapeutics passed the clinical trials and were finally approved for marketing by the regulatory agencies. Along with each phase, the percentage of efficient agents dramatically decreases. Generally, standard preclinical screening procedures for therapeutic agents involve identification of compounds from the 2D cell culture system tests and animal model tests and then to the introduction of clinical trials. The irrelevant 2D environment may provide misleading results regarding the predicted responses of cancer cells to anticancer drugs. The first drawback of a 2D cell culture systems is that an actual three-dimensional (3D) environment in which cancer cells reside in vivo is not accurately mimicked. However, various drawbacks and limitations are still of concern. The 2D cell culture systems are easy, convenient, cost-effective, and widely used. For testing the capability of novel anticancer drugs, the experiments are performed on cell-based assays, which offer information about cellular responses to drugs in cost/time effective and high throughput manners.Ĭurrently, two-dimensional (2D) platforms in which flat monolayer cells are cultured is still the most commonly used for the research of cell-based assays. ![]() ![]() Among them, drug discovery could be one of the most important approaches aiming to identify and verify new and potent anticancer agents for both daily medication and chemotherapy. Considerable efforts have been intended to develop effective approaches to cure cancer. Cancer is one of the most serious diseases causing almost one in six deaths globally, which is estimated to equal 9.6 million deaths in 2018. ![]()
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