More on the Development of Recellularized Lungs

Work on decellularizing different types of tissues to produce patient-matched donor organs proceeds at different rates. Some are much harder than others, not in the step of removing cells from the donor organ, which is fairly consistent for all tissue types, but in the development of methodologies to repopulate the tissue with all of the necessary cell types while ensuring that the correct tissue structures are produced. Last year researchers demonstrated a first pass at recellularized lungs, and suggested that there is a decade to go yet before they'll be ready for human use. More work is underway:

A promising option to increase the donor organ pool is to use allogeneic or xenogeneic decellularized lungs as a scaffold to engineer functional lung tissue. Decellularization of mouse, rat, goat, sheep, pig, non-human primate and human lung tissue has been accomplished, and resulted in three-dimensional acellular scaffolds that are generally devoid of detectable residual DNA. Repopulation of decellularized lungs has been reported using a number of different cell types. However, only partial recellularization of alveoli, airways and pulmonary vasculature has been achieved.

One potential approach to improve recellularization of decellularized lung scaffolds is to use the dynamic rotating wall vessel (RWV) bioreactor, which has been shown to promote growth and differentiation of stem and/or epithelial cells. The RWV is an optimized form of continuous suspension culture wherein cells are cultured in horizontally rotating bioreactors that are completely filled with media. The bioreactor rotation offsets sedimentation, creating a constant, gentle fall of cells and their growth substrate/scaffolds through the culture medium.

We demonstrate that decellularized mouse lungs recellularized in a rotating wall vessel contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total RNA compared to static recellularization conditions. These results were observed with two relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells. In addition, MSCs cultured in decellularized lungs under static but not bioreactor conditions formed multilayered aggregates. Gene expression and immunohistochemical analyses suggested differentiation of MSCs into collagen I-producing fibroblast-like cells in the bioreactor, indicating enhanced potential for remodeling of the decellularized scaffold matrix. In conclusion, dynamic suspension culture is promising for enhancing repopulation of decellularized lungs, and could contribute to remodeling the extracellular matrix of the scaffolds with subsequent effects on differentiation and functionality of inoculated cells.



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