Regenerating the nephron with human pluripotent stem cells

Nephrogenesis in humans is limited to the period of embryonic kidney development in utero, with no new nephrons formed after birth. Although the kidneys possess the capacity to self-repair segments of the nephron, nephron loss from acute or chronic kidney injury is irreversible and results in impaired function. Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, are an attractive source of cells to regenerate nephron progenitor cells (NPCs) and ultimately functional kidney tissue. NPCs are found exclusively during the period of embryonic development, but their nephron-forming capacity makes them an ideal cell population to regenerate with PSCs.

Significant progress has been made in the effort to direct the differentiation of human PSCs into NPCs. Differentiation protocols designed to recapitulate the complex process of kidney organogenesis in vitro can generate cells that express characteristic NPC markers and these cells can assemble into three-dimensional nephron-like structures. Additional studies are required to evaluate the functionality of these putative kidney cells and to test their ability to integrate into three-dimensional organized kidney tissue structures, either spontaneously or facilitated by bioengineered structures or scaffolds with appropriate matrix materials.

The successful recreation of human nephrons from PSCs would offer a novel therapeutic approach to treating patients with kidney disease.