Effect Of Modeling Intestinal Crypts As Cylinders For Simulating Stem Cell Dynamics Within Mouse And Human Colonic Crypts

To simulate the cell dynamics within mouse and human colonic crypts, many computational models have been developed. While real colonic crypts are shaped like test tubes, crypts were assumed as cylinders in several such models. However, possible drawbacks by modeling the crypt as a cylinder have not been investigated. Here we constructed a model considering a test-tube-like-shaped crypt in three-dimensional space, and simulated cell dynamics within it. The simulation results were compared with those obtained with a model using a cylinder crypt. We found that these two models showed different simulation results for the dynamics of expansion of a mutation occurred in a stem cell at the crypt bottom, and that the model using a test-tube-like-shaped crypt simulated the stem cell expansion more accurately. To simulate cell dynamics occurred in the lower part of the crypt, such as apoptosis and initial expansion of mutation, using a test-tube-like-shaped crypt is preferable. In a model assuming a cylinder crypt, it is considered that reported values for the required time of monoclonal conversion in a colonic crypt and its occurrence rate were overestimated and underestimated, respectively.