Transplantation of Human Induced Pluripotent Stem Cell-Derived Airway Epithelia at Different Induction Stages into Nude Rat.

Abstract

Tracheal reconstruction is necessary in patients with large tracheal defects. Previously, artificial tracheae made of polypropylene and collagen sponge have been used clinically by our group. As a basic research aimed at promoting epithelialization for infection defense, we transplanted cell sheets of human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (iAECs) with artificial tracheae into tracheal defects of rats and confirmed their engraftment. In this study, we examined the difference in the cell engraftment between hiPSC-derived airway epithelial progenitor cells (iAEPCs) and iAECs. Cell sheets were collected on days 38, 45, and 56 of induction into iAECs, then transplanted into nude rats with tracheal defects along with the artificial trachea. Two weeks after transplantation, surviving human nuclear antigen (HNA)-positive epithelial cells were observed none of six rats in the 38-day group, two out of six in 45-day group, and five out of six in the 56-day group. The proportion of surviving HNA+ cells among the epithelial cells of 56-day group was significantly higher those of 38-day group. Differentiated iAECs are more suitable for the transplantation of hiPSCs into tracheal defects. Our findings propose the use of differentiated cells for improvement of engraftment efficiency.