Recapitulating the microenvironment to increase the predictive validity of cell culture
Strides in recapitulating more ‘human’ environments in the lab setting will lead to much more predictively valid tests. An enabling technology here could increase the calibre of drugs that enter the clinic.
There’s a groundswell of enthusiasm for laboratory models that better mimic the ‘human’ state. This has played out in a wide array of ex vivo cell culturing companies such as Pear Bio, Oncoprecision, NeuScience, Genoskin, Kiyatec and many more. The ex vivo culturing allows for patients’ cells to be directly tested for drug efficacy, circumventing the proxy research and biomarkers that have been historically used. Ultimately the mecca of biomedical research would be to have an organoid for each human which takes into account each cell type. From this personalized dosing of drugs and maybe even n=1 drugs could be formulated for just you.
In our current system, drugs have been made for large patient populations but the ex vivo companies provide a portal to the future. Between now (drugs for the masses) and the future (drugs for individuals) ex vivo cell culturing companies will lead the way.
Importantly, all of these companies and the ones to come need to be in systems which mimic the human environment e.g. where metabolites, sugars, pH are consistent, not in flux as is the way with our current cell culturing techniques. This can be achieved via perfusion systems which exchanges cell culture media - keeping the nutrients and carbon sources consistent. However perfusion systems are historically lower throughput which leads to issues with replicate numbers and reproducibility. A recent paper by Kang et al., 2023 demonstrates the ability of researchers to now have 3D cell culture models which are much higher throughput and benefit from consitent conditions from being inside a perfusion system.
Some perfusion systems are also able to create shear stress which is important for cell phenotypes such as endothelial cell alignment, differentiation of stem cells to endothelial cells and the formation of actin stress fibers. Perfusion culture allows scientists to replicate the blood supply of cancer tumors. There’s also mechanotransduction cultures which can drive pressure forces onto cells since bones, muscles, and skin are all under various pressures throughout our days. Other methods such as ex vivo matrix-collagen-based cultures can recapitulate mouse development at certain stages.
