Scientists Engineer Functional Ureter Tissue from Stem Cells

A research team at Kumamoto University in Japan has successfully engineered functional ureter tissue from pluripotent stem cells, marking a significant advancement in regenerative medicine. This breakthrough brings scientists closer to developing fully transplantable kidneys capable of both urine production and expulsion, addressing a long-standing challenge in organ research.

The Role of Ureter Tissue in Kidney Function

The ureter is essential in the human urinary system, serving as the conduit for urine to flow from the kidneys to the bladder. Although progress has been made in creating kidney organoids, many of these models have lacked a functional ureter. Without this critical component, even sophisticated kidney organoids cannot replicate full organ function, limiting their applicability in transplantation or disease modeling.

Led by Professor Ryuichi Nishinakamura from the Institute of Molecular Embryology and Genetics, the team at Kumamoto University has successfully addressed this gap. By generating ureter tissue that mimics the structure and function of the natural organ, they have opened new avenues for the development of transplantable kidney systems.

Engineering Ureter Tissue from Stem Cells

The researchers utilized pluripotent stem cells—cells with the potential to develop into any cell type—to create the ureter tissue. Their innovative approach involved integrating two key components: ureteral stromal progenitors and epithelial cells. These were derived from either mouse embryos or induced from stem cells to form ureteral epithelial progenitors. When combined, these cell types self-organized into three-layered structures resembling natural ureters.

Notably, some of the lab-grown structures demonstrated rhythmic, wave-like contractions, closely mimicking the peristaltic motion that propels urine through the ureter. This feature not only showcases the functional capability of the engineered tissue but also underscores the potential for creating complete urinary systems in laboratory settings, a long-standing goal in the field of regenerative medicine.

In addition to organ development, the engineered ureter tissue serves as a valuable platform for studying genetic and congenital disorders. The researchers modeled a genetic condition linked to mutations in the TBX18 gene, known to affect ureter development. Organoids with this mutation exhibited impaired tissue formation, allowing scientists to observe and analyze developmental disruptions in a controlled environment. This modeling capability enhances understanding of congenital urinary tract disorders and could facilitate treatment testing.

This achievement is part of a broader initiative titled “International Leading Research: Creating A Kidney,” funded by the Japan Society for the Promotion of Science (JSPS). The project aims to develop fully functional, transplantable kidney organoids and is based at Kumamoto University, with collaboration from an international network of scientists. By merging the newly developed ureter tissue with previously created kidney organoids, researchers are advancing toward constructing artificial kidneys that can perform all functions of their natural counterparts, including urine production and excretion.

As this research progresses, it holds promise not only for transplant science but also for a deeper understanding of urinary system disorders. The ongoing work at Kumamoto University exemplifies the potential of regenerative medicine to revolutionize organ transplantation and treatment methodologies.