Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays
Name
sciadv.adj9793.pdf
Description
Published version
Size
13.49 MB
Format
Adobe PDF
Checksum (MD5)
4dc82c3df8652fffae9ccac8fd27c47c
Author(s)
Clift, Cassandra L
Blaser, Mark C
Gerrits, Willem
Turner, Mandy E
Sonawane, Abhijeet
Pham, Tan
Andresen, Jason L
Fenton, Owen S
Grolman, Joshua M
Campedelli, Alesandra
Date Issued
February 28, 2024
Journal
Science Advances
Publisher
American Association for the Advancement of Science
Citation
Cassandra L. Clift et al. ,Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays.Sci. Adv. 10, eadj9793 (2024).
Version
Final published version
Abstract
In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD because of the paucity of (i) appropriate experimental models that recapitulate this complex environment and (ii) benchmarking novel engineered aortic valve (AV)–model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)–bioprinted into 96-well arrays. Liquid chromatography–tandem mass spectrometry analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model versus traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% versus 70% of 2D proteins). Integration of cellular and vesicular datasets identified known and unknown proteins ubiquitous to AV calcification. This study explores how 2D versus 3D-bioengineered systems recapitulate unique aspects of human disease, positions multiomics as a technique for the evaluation of high throughput–based bioengineered model systems, and potentiates future drug discovery.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Chemical Engineering
Institute for Medical Engineering and Science
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution-Noncommercial
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/sciadv.adj9793
