Leveraging the model-experiment loop: Examples from cellular slime mold chemotaxis.

Interplay between models and experimental data advances discovery and understanding in biology, particularly when models generate predictions that allow well-designed experiments to distinguish between alternative mechanisms. To illustrate how this feedback between models and experiments can lead to key insights into biological mechanisms, we explore three examples from cellular slime mold chemotaxis. These examples include studies that identified chemotaxis as the primary mechanism behind slime mold aggregation, discovered that cells likely measure chemoattractant gradients by sensing concentration differences across cell length, and tested the role of cell-associated chemoattractant degradation in shaping chemotactic fields. Although each study used a different model class appropriate to their hypotheses - qualitative, mathematical, or simulation-based - these examples all highlight the utility of modeling to formalize assumptions and generate testable predictions. A central element of this framework is the iterative use of models and experiments, specifically: matching experimental designs to the models, revising models based on mismatches with experimental data, and validating critical model assumptions and predictions with experiments. We advocate for continued use of this interplay between models and experiments to advance biological discovery.

Injectable Therapeutic Organoids Using Sacrificial Hydrogels.

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method-by making use of the dynamic nature of hydrogels-could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.