Close
Enter your
text here

Creation of Patient-Derived Induced Pluripotent Stem Cell Lines for Studying Rare Pediatric Genitourinary Disorders

Creation of Patient-Derived Induced Pluripotent Stem Cell Lines for Studying Rare Pediatric Genitourinary Disorders 1024 683 Lauren Dembeck

Nationwide Children’s researchers create first-ever stem cell lines for rare genitourinary conditions.

Induced pluripotent stem cells (iPSCs) have revolutionized medical research by providing powerful tools to study disease mechanisms, especially in rare genetic conditions. These versatile cells, derived directly from patients that have the condition, offer unprecedented opportunities to uncover the underlying genetic and cellular abnormalities responsible for birth defects.

Researchers at Nationwide Children’s Hospital have recently generated the first iPSCs from children with two distinct and rare genitourinary conditions: prune belly syndrome and posterior cloaca (Type B). Their findings were published in the journal Stem Cell Research.

“Studies using these induced pluripotent stem cell lines will allow us to better understand the underlying causes of these conditions,” says pediatric urologist Linda Baker, MD, co-director and principal investigator in the Kidney and Urinary Tract Center at Nationwide Children’s and clinical professor of Urology at The Ohio State University. “They hold promise for developing therapeutic strategies beyond current surgical treatments, including potential gene therapies and medications aimed at correcting or even preventing these disorders during fetal development.”

In their studies, Dr. Baker and her outstanding research team successfully reprogrammed skin fibroblast cells derived from a 1-month-old male with prune belly syndrome and a 4 year and 8-month-old female with posterior cloaca (type B). Both iPSC lines exhibit typical pluripotent stem cell morphology, have normal karyotypes, express key pluripotency-associated proteins, and differentiate in culture into all three germ layers — the hallmark of pluripotent stem cells.

Prune Belly Syndrome

Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare congenital myopathy primarily affecting males. It varies in severity from mild to life-threatening and is characterized by three primary pathological features: a wrinkled, flaccid belly (ventral abdominal wall) with skeletal muscle deficiency; dilated urinary tract with poorly contractile smooth muscle; and severe intra-abdominal undescended testes.

“During normal fetal development, the bladder cycles between filling and emptying, crucially maintaining amniotic fluid,” explains Dr. Baker. “However, in PBS, urine backs up in the bladder, risking kidney damage, reducing amniotic fluid, and adversely affecting the development of other organs, such as the lungs.”

Dr. Baker is internationally recognized for her expertise in PBS, having evaluated and cared for over 200 children with the condition. Her recent research aims to identify the genetic basis of the condition, to better understand bladder physiology and muscle underactivity, and to improve daily life of children with PBS.

“These iPSCs will enable us to study bladder smooth muscle cells directly, paving the way for new corrective approaches for affected children,” she says.

Posterior Cloaca (B)

Cloaca is an extremely rare and severe congenital anorectal malformation occurring exclusively in females, characterized by the convergence of the gastrointestinal, genital, and urinary tracts into a single channel. Posterior cloaca (Type B) is an even more uncommon subtype of this condition, in which the opening of the urogenital sinus is located immediately anterior to the anus.

“The clinical implications of cloaca are serious,” explains Dr. Baker, a specialist in complex genitourinary reconstruction. “Patients commonly experience urinary incontinence, kidney failure, reproductive tract obstruction , and severe constipation or fecal incontinence.”

The research team established the iPSC line from a posterior cloaca patient as a community resource, aiming to foster detailed mechanistic studies and advance our understanding of the developmental origins of cloaca in humans.

 

References

  1. Gomez Limia CE, Albert K, Basnet K, Atre C, Malik H, Streeter DL, Amado NG, Baker LA. Generation of induced pluripotent stem cell line, NCHi028-A, from a male child with Prune Belly Syndrome. Stem Cell Res. 2025 Apr;84:103681. doi: 10.1016/j.scr.2025.103681. Epub 2025 Feb 13. PMID: 40022902.
  2. Gomez Limia CE, Albert K, Atre C, Basnet K, Streeter DL, Amado NG, Baker LA. Generation of induced pluripotent stem cell line, NCHi027-A, from a female child with Posterior Cloaca (Type B). Stem Cell Res. 2025 Feb;82:103636. doi: 10.1016/j.scr.2024.103636. Epub 2024 Dec 19. PMID: 39709757.

Image credit: iStock

About the author

Lauren Dembeck, PhD, is a freelance science and medical writer based in New York City. She completed her BS in biology and BA in foreign languages at West Virginia University. Dr. Dembeck studied the genetic basis of natural variation in complex traits for her doctorate in genetics at North Carolina State University. She then conducted postdoctoral research on the formation and regulation of neuronal circuits at the Okinawa Institute of Science and Technology in Japan.

You might also like