How do we get there?

[Stephen Riffle]

What will it take to dethrone animal models as the gold standard in preclinical drug testing?

For almost a century, animals have served as the last line of defense in drug development, and for good reason: unlike in vitro systems, living animals have interconnected organ systems and complex tissues that interact with—and potentially alter—drug behavior. There is no doubt that animals are valuable, but they are also fallible. Among their many limitations, mice, dogs, primates, and all other animal models are genetically distinct from humans in important ways—ways that can affect how the body processes and responds to therapeutics.

No model system will be perfect, but it seems like Organ-Chips, spheroids, and other 3D models have the potential to overtake animals as the gold standard. These in vitro systems can be designed to incorporate heterogeneous populations of human cell lines; they can recreate 3D gradients and cell-cell interactions; and, in the case of MPS/Organ-Chips, they can integrate biomechanical forces that emulate fluid flow and muscle contraction.

As we continue to build on and improve these models, the prospect of using 3D models in place of animal models becomes ever more realistic. But, we’re not quite there yet.

So, how do we get there? What do we as a field need to demonstrate or build in order to (1) achieve widespread recognition of the value of 3D models for preclinical drug testing; (2) challenge the supremacy of animal models in this space; and (3) replace animal models with 3D counterparts where necessary?

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