The application of three-dimensional (3D) tumor models in life sciences has gained increased attention, especially in pharmaceutical research. This is because 3D tumor models represent physiological conditions of the tumor microenvironment better, making them potentially useful for guiding studies on drug screening. In addition, in terms of cell–cell/cell–extracellular matrix communication and spatial arrangement of tissues, 3D tumor models surpass the conventional two-dimensional (2D) cell culture systems. Despite these advantages, drug testing is still being conducted using 2D cancer cell models. Previous studies have demonstrated various techniques that have been proven to be effective in growing cancer cells in 3D, however the procedures are time consuming, complex and expensive.
To address this challenge, Bisan Samara, Muhammedin Deliorman, Pavithra Sukumar and led by Professor Mohammad A. Qasaimeh from the Division of Engineering, New York University Abu Dhabi developed a new technology through which high throughput arrays of 3D tumor models can be created on a single paper platform for drug screening applications. The newly developed paper-based 3D tumor arrays was successfully cryopreserved and thawed for on-demand use. The research work is published in the Journal Lab on a Chip.
The research team simplified the technology that the entire paper patterning and consequent cell loading process took about 15 to 20 min. In their study, they optimized the mask dimensions, the patterning process, and characterized the paper platform for additional functional parameters.
In their developed platform, the growth rate of a breast cancer cell line 3D culture was found to be highest in serum-free media compared to their growth rates in 5, 10, 30, and 50% serum media. The authors also reported that the direct culture of the paper platform in serum-free media resulted in an exponential growth of the 3D culture of more than 7-fold increase. Similarly, when the paper platform was cryopreserved, then thawed and cultured in serum-free media, a 6-fold increase in growth was observed. The extension of the incubation of paper in culture medium for up to 14 days for both cultured and cryopreserved conditions had no significant effect on the size of the microspots.
The team found that the chemotherapeutic drug cisplastin had a greater dose- and time-dependent effect on 2D cells of human breast cancer cell line MCF-7 compared to the 3D culture formed within paper microspots. In addition, the effect of cisplatin was found to be similar for 3D aggregates that were thawed and cultured following their cryopreservation. In contrast and as expected, the human breast cancer cell line MDA-MB-231 cells displayed an obvious resistance to cisplastin in both 2D cultures and 3D models.
Through this landmark study, the authors have developed a new technology for the creation of 3D tumor models that has a lower cost with an easier and faster experimental process compared to existing processes. They have also shown that patterned 3D tumor arrays can be successfully cryopreserved for prolonged periods and thawed for on-demand use. The results of the study can advance the development of personalized medicine and tissue engineering.
Samara B, Deliorman M, Sukumar P, Qasaimeh MA. Cryopreservable arrays of paper-based 3D tumor models for high throughput drug screening. Lab Chip. 2021 Mar 9;21(5):844-854.Go To Lab Chip