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Primary Human Cell-Derived Extracellular Matrix from Decellularized Fibroblast Microtissues with Tissue-Dependent
Vera C Fonseca1, Vivian Van1, Blanche C Ip1,2
1Department of Pathology & Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912 USA.
Cellular and Molecular Bioengineering
|July 25, 2024
Summary
Researchers developed a method to create human tissue-specific extracellular matrix (ECM) using engineered microtissues. This decellularized ECM biomaterial mimics native tissues and supports cell growth, offering potential for personalized regenerative medicine.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Human extracellular matrix (ECM) is complex and difficult to replicate.
- Current methods using fibroblasts on rigid surfaces can alter ECM production.
- Reversing engineering native ECM is crucial for understanding tissue function and disease.
Purpose of the Study:
- To develop a method for producing decellularized ECM from human fibroblasts that mimics tissue and disease-specific features.
- To investigate the impact of engineered microtissue formation on ECM characteristics.
- To create a versatile platform for generating personalized biomaterials.
Main Methods:
- Primary human cardiac and lung fibroblasts were cultured in low-adhesion microwells to form engineered microtissues.
- Microtissues were decellularized to create acellular ECM biomaterials.
- Morphological, architectural, mechanical, transcriptomic, and proteomic analyses were performed.
Main Results:
- Microtissues exhibited tissue-specific gene expression and proteomic profiles, closely resembling native ECM.
- Distinct collagen architectures were observed between healthy lung (web-like) and heart (dense) microtissues.
- Decellularized ECM showed physiologically relevant mechanical stiffness and supported cell viability and proliferation.
Conclusions:
- Engineered microtissues provide a method to generate human, tissue- and disease-specific decellularized ECM.
- This approach enables the creation of personalized matrices that recapitulate native tissue states.
- The generated ECM holds promise for ex vivo cell culture and therapeutic implantation.
