TY - JOUR
T1 - Recellularization of decellularized lung scaffolds is enhanced by dynamic suspension culture
AU - Crabbé, Aurélie
AU - Liu, Yulong
AU - Sarker, Shameema F.
AU - Bonenfant, Nicholas R.
AU - Barrila, Jennifer
AU - Borg, Zachary D.
AU - Lee, James J.
AU - Weiss, Daniel J.
AU - Nickerson, Cheryl A.
N1 - Publisher Copyright:
© 2015 Crabbé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/5/11
Y1 - 2015/5/11
N2 - Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), 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 (C10). 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.
AB - Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), 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 (C10). 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.
UR - http://www.scopus.com/inward/record.url?scp=84930683942&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0126846
DO - 10.1371/journal.pone.0126846
M3 - Artículo
C2 - 25962111
AN - SCOPUS:84930683942
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e0126846
ER -