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In this Research Strategy, tissue is decellularized in the lab leaving a bio-scaffold in place that is then altered or recellularized to restore lost function. The decellularization process mostly preserves the structure and components of the extracellular matrix while removing the cellular components from cadaveric organs or tissues. The extracellular matrix plays a major role in guiding cell-cell and cell-organ interactions and drastically vary from organ to organ.
The advantage of decellularized bio-scaffolds is that they mostly retain the micro- and macro-architecture and vascular conduits of native tissues and organs; they mostly preserve intrinsic biochemical cues for guiding cell retention or survival, migration, and differentiation, which are key requirements for successful recellularization; and they can be obtained from xenogenic sources and repopulated with patients’ own cells.
In recent years, numerous human-scale organs have been successfully decellularized with low remnant DNA content using different decellularization protocols; however, no method is recognized as optimal due to variability in tissue composition. Thrombosis and inflammation is another challenge for decellularized organs, which can be overcome by complete endothelialization of blood-contacting surfaces.
Important parameters for recellularization are cell type, cell numbers, and cell seeding strategies. Recellularization involves the seeding of vascular, parenchymal, and support cells into a previously decellularized scaffold. Most decellularized organs need to be at least, partially recellularized prior to implantation as the number of cells recruited is likely to be insufficient to repopulate the entire tissue/organ. Successful recellularization of de-cell scaffolds remains challenging. Additional hurdles to be addressed are: cells delivery methods, designing cost-efficient GMP compliant cell culture media that works across multiple cell types, building bioreactors that will provide the necessary milieux for growing organs, in-line monitoring tools that can provide both real-time physiologic parameters and provide release criteria for these bioengineered constructs.
The work of the New Organ Research Alliance's De-Cell / Re-Cell Scaffolding Committee helps to identify and clarify significant challenges and sub-challenges associated with the decellularization and recellularization techniques and find solutions to these challenges to create a functional and reproducible tissue-engineered product. See our committee members here.