Direct conversion of fibroblasts into urothelial cells that may be recruited to regenerating mucosa of injured urinary bladder
Authors
Yuta Inoue, Tsunao Kishida, Shin-ichiro Kotani, Mika Akiyoshi, Hideto Taga, Makoto Seki, Osamu Ukimura, Osam Mazda
Institution
Kyoto Prefecture University of Medicine
Country
Japan
Year
2019
Journal
Scientific Reports
Abstract
Urothelial cells play essential roles in protection of urine exudation and bacterial invasion at the urothelial mucosa, so that defect or damage of urothelial cells associated with urinary tract diseases may cause serious problems. If a sufficient number of functional urothelial cells are prepared in culture and transplanted into the damaged urothelial lesions, such technology may provide beneficial effects to patients with diseases of the urinary tract. Here we found that human adult dermal fibroblasts were converted into urothelial cells by transducing genes for four transcription factors, FOXA1, TP63, MYCL and KLF4 (FTLK). The directly converted urothelial cells (dUCs) formed cobblestone-like colonies and expressed urothelium-specific markers. dUCs were successfully expanded and enriched after serial passages using a specific medium that we optimized for the cells. The passaged dUCs showed similar genome-wide gene expression profiles to normal urothelial cells and had a barrier function. The FTLK-transduced fibroblasts were also converted into urothelial cells in vivo and recruited to the regenerating urothelial tissue after they were transplanted into the bladder of mice with interstitial cystitis. Our technology may provide a promising solution for a number of patients with urinary tract disorders.
Product use
Conversion of fibroblasts to urothelial cells
Tissue type
Bladder
Tissue info
(aHDFs transduced with FTLK and cultured in CnT-Prime medium in laminin-coated plates) were referred to as the directly converted urothelial cells (dUCs)