Drug development with an added dimension

Cellular responses to drug treatments in 3D cultures have been shown to be more similar to what occurs in vivo compared to 2D culture. A number of studies have found that cells cultured in 3D models are more resistant to anticancer drugs than 2D cultures. For example, ovarian cancer cell survival and proliferation in 3D cultures after paclitaxel treatment was reduced by 40% or 60% in 3D cell spheroids, while the same treatment led to 80% reduced cell viability in the 2D cell monolayer. Karlsson et al. studied the drug sensitivity of colon cancer HCT-116 cells in a 3D spheroid and 2D monolayer model in response to four standard anticancer drugs (melphalan, 5-FU, oxaliplatin, and irinotecan) and two promising investigational cancer drugs (acriflavine and VLX50; ). The results indicated that all drugs were highly active in 2D monolayer culture but generally less active and gradually lost their activity in 3D spheroids (6 day spheroids were more resistant than 3 day spheroids in ), irrespective of different action mechanisms, suggesting that the geno- and phenotypical changes induced by 3D spheroids formation were associated with the increased drug resistance. The stronger drug resistance in 3D culture results primarily from signals from dynamic cellular interactions between neighboring cells and ECM input into the cellular decision-making process. The increased drug resistance in 3D culture can also be attributed to limited diffusion through the spheroid and to hypoxia, which has been shown to lead to the activation of genes involved in cell survival and drug sensitivity. Such chemoresistance developed in 3D spheroids is observed in vivo as well. A study using multicellular 3D culture of liver tumor cells as an in vitro model to test anticancer drugs further found that stromal cells also played a role in drug resistance of cancer cells.

It is increasingly evident that 3D cell culture models are better models than the traditional 2D monolayer culture due to improved cell–cell interactions, cell–ECM interactions, and cell populations and structures that resemble in vivo architecture. In the past several years, a huge variety of 3D cell culture systems have been created as experimental tools for diverse research purposes. There is no doubt that 3D culture systems hold great promise for applications in drug discovery, cancer cell biology, stem cell research, and many other cell-based analyses and devices, by bridging the traditional 2D monolayer cell culture to animal models. While the 3D cell culture models are currently widely studied in academia with a focus on creation of 3D systems with excellent biological relevance, there are still many hurdles that must be overcome before these systems can be widely accepted in industry. Recent developments clearly indicate that the transition from 2D to 3D cell cultures for industry applications is promising, but the maturity of the technology and the cost are still the main concerns in making this transition possible. Much effort is still needed to assure reproducibility, high throughput analysis, compatible readout techniques, and automation in order to establish standardized and validated 3D cell culture models.

for more infos see reference:

https://europepmc.org/articles/PMC4026212