We’ve Been Developing Pharmaceuticals Wrong for over 100 years
Updated: Nov 18, 2020
100-year-old methods of 2D cell culture are a wildly inaccurate, error prone methodology for drug development and cell biology research.
Neary every therapeutic on the market started in a 2D cell culture dish. This is convenient and significant work-flows have been designed around these systems, however there are massive casualties to show for it.
Billions of dollars are lost in pharmaceutical development due to false positive results. Value capture of a developmental pipeline is likely spotty, if not dismal due to false negative results produced by 2D culture screening.
Finally, patients suffer from poor approximations of toxicology and efficacy in both animal models and 2D cell culture.
In a recent study, six independent laboratories demonstrated the importance of 3D culture for liver toxicity testing; 2D culture failed to replicate real in vivo results.
Cells behave as expected in 3D tissue or tissue-like structures. But in 2-dimensional cultures? All bets are off.
So much so that a couple hours after taking a tissue sample and putting it into standard cell culture conditions, human cells change their fundamental characteristics and lose native function and the ability to serve as an accurate read-out for human toxicology and drug development.
With overwhelming evidence that 3D tissue culture provides better results for toxicology and research scientists are re-thinking the 100-year-old paradigm. In recent years development of organ on a chip models and 3D spheroid culture have tried to move scientists closer to real human tissue toxicology.
Despite all of this traditional 2D cell culture remains the standard.
The problem is, there has been no way for cell biology or R&D labs to reproducibly create 3D scaffolds that are effective in supporting tissue growth. Spheroids (small compressed bundles of cells) are difficult to work with, do not always form spontaneously, and can take a month or more to grow. Organ on a chip models also have high failure rates and require specialized knowledge.
Without access to 3D tissue scaffolds that have circulation or microvasculature as architecture, scientists haven’t been able to grow dense cell-laden tissue — the type needed to support the cell-cell interactions that drive gene expression and phenotypic development — larger than 300 micrometer spheroids (the limit of oxygen diffusion in a tissue). 3D tissue scaffolds that match human-sized vasculature and were large enough to generate meaningful results, until now, were simply impossible to build.
3D Human Cell Culture: Revolutionary Tools and Approaches
The holographic bioprinters (Holograph-X produced and sold by Cell Ink) will allow for researchers to design and build pre-vascularized tissue structures that match human tissue or simply design their own.
A 3D scaffold allows cells to function as they do in their native environments, providing a powerful tool for everything from therapeutics development to transplant medicine.
With the Holograph-X real tissue structures can be re-created with consistency and the ease of loading an ink, starting a program, and walking away. The structures are then washed in cell media.
Cells can be seeded within an hour by either pipetting them on top of the structure for adherent cells, or pipetting a droplet of cells suspended in the biomatrix of the researchers choice. The cell laden structures are then ready for drug testing or animal transplantation.
Transplantation of human tumors into animal models is routinely successful (100% success rate) with only 150,000 cells 12 hours after seeding. These results were replicated in both collagen I and matrigel cell slurries.
Printing pre-vascularized tissue structures for human cell culture will not only save money and compress drug development timelines but will protect people in Phase I studies by more closely replicating toxicology in human tissues before a clinical trial.
The ability to engineer real human tissue — with vasculature, to scale — will also reduce the number of animals used in animal testing and will likely improve the engraftment in patient derived xenograft (PDX) models used for studying human tumors in animals. In some areas, animal testing may be eliminated by access to viable human tissues.
If you have such powerful technology why share?
I’ve been asked many times;
“Why would you take this idea, this phenomenal advancement, and release for others to use?”
When I turn to answer this question, I have the same imperative sense of a need to take action that I did when I started this company: this technology and the power of it is too important.
If I were to wake up and have a company the size of Pfizer, Bayer, or Genetech tomorrow, we still wouldn’t have the bandwidth to use 3D culture systems and this technology to its fullest potential.
The applications in human tissue engineering are nearly endless. The faster we can drive adoption, the sooner we will have a universal win for all of us.