John Sauld 10/24/2022 at 9:53 am
Is anyone attempting to compare drug responses between an Organ-Chip/spheroid/organoid that models mouse tissue vs the actual in vivo tissue response?
I ask because it was recently suggested that this type of study would be important—maybe even critical—for Organ-Chips to overtake animal models as the gold standard in drug development. This was briefly highlighted in a recent review from Don Ingber, saying:
“There is also increasing recognition of the need to create Organ-Chip models made with cells from other species (for example, rodents, dogs or NHPs) to generate benchmark comparison data that could help pharmaceutical companies and vaccine developers to validate results obtained in these models relative to results obtained in past in vivo studies, and thus become more comfortable with integrating Organ-Chips into their development processes”
On first principle, it makes sense as a way to demonstrate that 3D models are capable of accurately predicting in vivo processes. But, is this necessary given the growing body of evidence that suggests 3D models, when designed well, do accurately represent key features of in vivo tissues?
I’m curious how important you all think these experiments really are. Is it necessary to build animal-specific models simply to show that 3D systems accurately recreate in vivo conditions? Or do you think there is sufficient evidence for this already?
Lorna Ewart 11/22/2022 at 4:28 am
This is a great question John!
I recently read a paper in Frontiers in Bioengineering and Biotechnology that describes the creation of a murine bone marrow microenvironment (https://www.frontiersin.org/articles/10.3389/fbioe.2022.855777/full). The authors were able to maintain functional hematopoietic stem cells in vitro over a 14 day culture period. The chip recapitulated cell-cell interactions that occur in vivo and open the opportunity for mechanistic investigation of hematologic malignancies. But in response to your question, the authors agree. They end the paper stating that their chip demonstrated that it can be used to validate cellular phenotypes found within in vivo murine leukemic models and proposed that the in vitro environment of a similar human chip model will recreate human in vivo.
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