Cell encapsulation in PEG-fibrinogen hydrogels as a feasible tool for cell therapy in a mouse model of pneumonic plague

Recent advances in the field of cell therapy have proposed new solutions for tissue repair. However successful translation of such therapies into the clinic relies on the development of novel delivery strategies to increase cell viability and engraftment. Previously we reported that cell encapsulation in a semi-synthetic PEG-Fibrinogen hydrogel scaffold enhanced cellular functions and viability. Here we studied the feasibility to elicit this material technology for cell-based treatment in a model of pneumonic plague, a fatal disease caused by inhaled Yersinia pestis bacteria leading to overwhelmed inflammatory responses in the lung, sepsis and death. Although early antibiotic treatment is beneficial to treat pneumonic plague, severe tissue damage remains in the lung of recovering survivors. We demonstrated the encapsulation of donor type I epithelial cells and alveolar macrophages in an equivalent distribution within hydrogels, with similar viable qualities as each cell type apart. Encapsulated macrophages secreted moderate levels of TNF-a and were more viable compared with non-encapsulated cells in response to bacterial endotoxin exposure, demonstrating the protective microenvironment inside the hydrogel. The incubation of these encapsulated macrophages with whole lung extracts obtained from Y. pestis infected mice induced hydrogel degradation and cell migration towards the surrounding inflammatory environment. These results demonstrate the added value of cell encapsulation and reveal the potential use of hydrogels for cell delivery for therapy.