Simulation of lung alveolar epithelial wound healing in vitro.
The mechanisms that enable and regulate alveolar type II (AT II) epithelial cell wound healing in vitro and in vivo remain largely unknown and need further elucidation. We used an in silico AT II cell-mimetic analogue to explore and better understand plausible wound healing mechanisms for two conditions: cyst repair in three-dimensional cultures and monolayer wound healing. Starting with the analogue that validated for key features of AT II cystogenesis in vitro, we devised an additional cell rearrangement action enabling cyst repair. Monolayer repair was enabled by providing 'cells' a control mechanism to switch automatically to a repair mode in the presence of a distress signal. In cyst wound simulations, the revised analogue closed wounds by adhering to essentially the same axioms available for alveolar-like cystogenesis. In silico cell proliferation was not needed. The analogue recovered within a few simulation cycles but required a longer recovery time for larger or multiple wounds. In simulated monolayer wound repair, diffusive factor-mediated 'cell' migration led to repair patterns comparable to those of in vitro cultures exposed to different growth factors. Simulations predicted directional cell locomotion to be critical for successful in vitro wound repair. We anticipate that with further use and refinement, the methods used will develop as a rigorous, extensible means of unravelling mechanisms of lung alveolar repair and regeneration.
UCSF/UC Berkeley Joint Graduate Group in Bioengineering, University of California, Berkeley, CA 94720, USA.
Sean H J
SH
Kim
Michael A
MA
Matthay
Keith
K
Mostov
C Anthony
CA
Hunt
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D008168:Lung; D014945:Wound Healing / Q000502:physiology*