4.2 Article

Using biophysical cues and biomaterials to improve genetic models

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DOI: 10.1016/j.cobme.2023.100502

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Stem cells Extracellular matrix Genome editing Disease modeling,; Organoids.

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With the development of induced pluripotent stem cells and modern differentiation protocols, significant progress has been made in in vitro disease modeling, sometimes replacing animal models. However, the rigid cell culture substrates often used in vitro may limit the ability to fully reproduce human diseases. Recent studies suggest that combining biomaterials and advanced microphysiological systems with stem cells expressing disease mimicking genetics could greatly enhance current disease modeling efforts.
With the advent of induced pluripotent stem cells and modern differentiation protocols, many advances in our understanding of disease have been made possible by in vitro disease modeling; in some cases, their use may have supplanted animal models. Yet in vitro models often rely on rigid cell culture substrates that could limit our ability to completely reproduce human disease in a dish. Nascent work, however, suggests that the combination of biomaterials and/or advanced microphysiological systems-which better recapitulate tissue properties-with stem cells expressing disease mimicking genetics, could substantially improve current disease modeling efforts where genetics alone is insufficient. This review will highlight such recent advances as well as review current challenges that the fields must overcome to create more personalized therapeutics in the future.

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