Organoids Derived from Patients with Kidney Disease May Aid Research

Chicago—Stem cells from patients with polycystic kidney disease have been coaxed into growing into kidney-like structures, which may aid researchers studying the disease, according to a study presented at Kidney Week 2016.

Ryuji Morizane, MD, PhD, an instructor and scientist in the Brigham and Women’s Hospital Renal Division in Boston, and his colleagues presented data on how they grew the kidney-like structures, called kidney organoids. They also described the features of the kidney organoids and the disease features they recreate.

Improvements in cell culturing technology have allowed scientists to coax stem cells into growing into organoids that recapitulate many of the features of kidneys, lungs, the gut, brain, and retina (Clevers H. Cell 2016; 165:1586–97). Scientists can use organoids to study organ development and disease processes in the laboratory, noted Hans Clevers, MD, PhD, professor of molecular genetics at the Hubrecht Institute in Utrecht, Netherlands, in his review. Organoids derived from the cells of patients with diseases, in particular, hold the promise to aid personalized medicine, he noted.

Morizane and his colleagues had previously developed a method to grow kidney organoids from human pluripotent stem cells that have the basic features of the kidney, including segmented nephron structures containing podocytes, proximal tubules, loops of Henle, and distal tubules juxtaposed to interstitial cells. Now, they have applied this method to pluripotent stem cells collected from patients with autosomal recessive polycystic kidney disease (ARPKD). The patients’ cells grew into kidney organoids that had large cysts in the tubules, just like those seen in patients with ARPKD.

“Establishment of a novel platform to model ARPKD using human kidney organoids will facilitate studies on mechanisms of cyst formation and contribute to the development of chemical screening systems to find potential therapeutic agents for polycystic kidney disease,” said Morizane.

The work may also lay the groundwork for one day growing transplantable kidneys in the laboratory.

“Our organoid system enables in vitro studies of kidney pathophysiology, nephrotoxicity assays, and disease modeling, and ultimately will lead to development of bioengineered kidneys for regenerative medicine,” Morizane said.

Clevers said Morizane’s study builds on work by another laboratory that has generated kidney organoids from human stem cells (Takasato M, et al. Nat Proc 2016; 11:1681–1692). It also demonstrates the potential of stem cells to form remarkably organ-like structures.

“This beautiful study builds on earlier work by Melissa Little and her colleagues in Melbourne,” Clevers said. “It is amazing to witness again the self-organizing capacity of stem cells. The only thing missing from these mini-kidneys is the plumbing: blood vessels and ureter.”

“Kidney organoids derived from human pluripotent stem cells contain multiple kidney compartments and model polycystic kidney disease” (Abstract 2139).

December 2016 (Vol 8, Issue 12)