Tissue-Engineered Lungs for in Vivo Implantation
Thomas H. Petersen,1,2 Elizabeth A. Calle,1 Liping Zhao,3 Eun Jung Lee,3 Liqiong Gui,3 MichaSam B. Raredon,1 Kseniya Gavrilov,4 Tai Yi,5 Zhen W. Zhuang,6 Christopher Breuer,5 Erica Herzog,6 Laura E. Niklason1,3,*
Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 min), the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
1 Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
2 Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3 Department of Anesthesia, Yale University, New Haven, CT 06520, USA.
4 Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
5 Department of Surgery, Yale University, New Haven, CT 06520, USA.
6 Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
* To whom correspondence should be addressed. Email: laura.niklason@yale.edu
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