144 Chapter 6 non-disease and emphysematous decellularized lung tissue, although reduced growth factor production was observed in the latter [147]. These results clearly showed that the state of the ECM largely influences the cellular response and this response varies between different cell types. Another prominent chronic lung disease is asthma. The mechanisms involved in ECM remodeling in asthma have not been as thoroughly investigated using decellularized ECM models as IPF and COPD, reflecting the lack of available tissues from asthmatic donors for decellularization. Preliminary investigations using asthmatic equine models have indicated decreased levels of collagen I and fibronectin levels in bronchi-derived acellular scaffolds [148]. However future investigations of this model are warranted, albeit challenging. Decellularized lung scaffolds have also been used to model the tumor microenvironment. Decellularized rat lungs repopulated with human cancer cell lines and cultured in customized bioreactors, produced tumor nodules and expressed MMP 9, neither of which was evident in equivalent 2D models [149]. Interestingly, murine decellularized lung matrices supported the invasion and colonization of metastatic breast cancer cells while the majority of non-metastatic cells were unable to survive under the same conditions [150]. These models serve as powerful tools to understand cancer metastasis and in turn will provide platforms for assessing anticancer therapies. Whole lung decellularization for transplantation has been attempted by several research groups. However, these have mainly been restricted to animal models (rodents, porcine, and canine lungs) that have been recolonized for short periods with animal or human lung cells, and in some studies implanted in respective animal models to test compliance and functionality of the engineered lungs [151-160]. Whole human lung or lobe decellularization and recellularization is less frequent for obvious availability and ethical reasons [152, 161]. In addition, there are several recognized limitations that must be overcome to advance this application including the standardization of the patient-derived lung samples and using these scaffolds as in vitro models. Moreover, more advanced methods for testing the capacity of the gas exchange in a recellularized in vitro model are required to evaluate the efficiency of the recellularization process and subsequent functionality of the engineered lung. Decellularization presents a potent methodology for the development of in vitro models as age and injury induced changes in ECM composition and characteristic anatomical alterations were retained post decellularization of lungs reflective of the original disease state [153, 159, 162]. Extensive information about other factors influencing cellular behavior in response to decellularized scaffolds can be found
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