Development of Adult Renal Tubular Organoids from Different Human Individuals in a Single Medium.

Abstract

Introduction: Organoids are miniature organs developed through technology. Kidney organoids that originate from human inducible pluripotent stem cells (iPSCs) were developed to recreate renal diseases. However, it is impossible to simultaneously produce kidney organoids from iPSCs of multiple individuals and in a single medium. We herein report the development of adult renal tubular organoids, namely, "tubuloids," from primary renal epithelial cells from multiple human individuals in a single medium.

Methods: Kidneys from eight patients who underwent nephrectomy due to malignancy were sectioned, and primary renal epithelial tubule cells were cultured; four had normal kidney function, and four had mild chronic kidney disease (CKD). Growth factors and Matrigel were added to the primary culture.

Results: Primary cultured renal epithelial cells from normal kidneys exhibited a fine and swollen epithelial appearance, whereas those from kidneys with mild CKD were smaller and slightly elongated. Growth was faster in normal kidney cells than in mild CKD cells. At the beginning of the three-dimensionalization (day 0), normal renal tubuloids grew faster than mild CKD tubuloids. The difference in size between normal and mild CKD tubuloids was not obvious by day 5. Both tubuloid types had comparable sizes by day 21.

Conclusions: Renal tubular organoids can be developed simultaneously and in a single medium. Our method is expected to be used as a human pathological model.