UC Davis Children's Hospital researcher identifies candidate adult bladder stem cells
Researchers at UC Davis Children's Hospital have identified the potential stem cells that become the bladder, adding to the body of research that already has identified stem cells that can regenerate many of the body's other organs.
The finding is significant because it raises the hope that scientists may one day regenerate replacement bladder tissue for patients whose bladders are too small or don't function properly, such as children with spina bifida and adults with spinal cord injuries or bladder cancer.
"This is the first time that candidate adult stem cells of the lining of the bladder have been identified," said Eric Kurzrock, professor and chief of the division of pediatric urology at UC Davis Children's Hospital. "The main thing that we've done is characterized some of the protein expression on the outside of these cells and defined what they look like and how they are different from other cells of the bladder."
The finding is described in a paper published online in the American Journal of Physiology - Renal. The cells are good candidates for bladder, or urothelial, stem cells in part because they were found to have many of the qualities of stem cells discovered in other organs: They demonstrate superior "clonogenic and proliferative abilities."
What that means, Kurzrock said, is that when they are needed, these cells give rise to "daughter" cells that go out and replenish the urothelial tissue. The candidate urothelial stem cells were distinguishable from other bladder cells because they retained material used to "tag" or label them more consistently when compared to mature dividing cells in which the label material dissipates readily.
"Label-retaining cells have been identified as the tissue stem cells in skin, cornea, intestine and prostate," the study says. "We propose that label-retaining cells represent putative urothelial (bladder) stem cells."
"This is an important step," Nolta said. "Until now, no one had identified these cells that give rise to the bladder, and there are a lot of people who need replacement bladder tissue, like children with pathological conditions such as spina bifida and adults with spinal cord injuries or cancer."
— Jan Nolta, UC Davis Stem Cell Program Director
"What this means is that for children with many diseases where there is a problem with the bladder we may eventually be able to regenerate the tissue of the bladder," she said. "We are currently working on ways to bioengineer replacement organs using stem cells, and now, due to Dr. Kurzrock's interesting work, the bladder will be one of the candidates."
Kurzrock, who cares for children with spina bifida in his clinical practice at UC Davis as well as at Shriner's Hospital for Children and at other hospitals in the Sacramento region, said creating replacement bladder tissue could make a significant improvement in the quality of life for children with spina bifida and other patients with bladder disorders.
Spina bifida is one of the most common, permanently disabling birth defects in the United States, affecting one in 1,000 children, often leaving them unable to walk without the use of crutches, leg braces or wheelchairs. Most of these children are also unable to control their bowel and bladder function.
"When people see children and adults in wheelchairs due to spina bifida or spinal cord injury, they see that they have orthopaedic or neurologic ailments. But the one thing almost all of these patients have in common is loss of the function of their bowel and bladder," Kurzrock said.
"The average person thinks 'These children only have problems with walking.' But one of their major issues is the inability to empty their bowels and bladders, which dramatically affects their quality of life," he said.
Kurzrock also treats children with bladder exstrophy, a rare condition in which a portion of the bladder protrudes from the abdomen, as well as congenital defects of the reproductive organs.
"Most of what I do in my clinical practice is reconstructive surgery," he said. "I need a lot of tissue to rebuild things. If we could bioengineer new bladder replacement tissue that would be great because today we use bowel and stomach tissue."
The use of bowel tissue to reconstruct the bladder tissue is problematic because it requires additional surgery and therefore increases complications. And the bowel and stomach have different properties that make them less than ideal for use in the bladder.
"The bladder is not absorbent. It's created to hold waste products from your body — the ammonia and the nitrogen — and let it sit there for four hours or eight hours overnight and not absorb any of it," Kurzrock said. "You need a lining in your bladder and in your ureter that is non-absorbent."
Bowel is made for absorbing nutrients. It also makes mucous that helps it to pass waste. Having mucous in urine is problematic because it creates infection and stones in the urinary tract. In addition, physicians have begun to see anecdotal cases of bladder cancer in bladders reconstructed from bowel tissue.
Kurzrock said that regeneration of bladder tissue is a good possibility because bladder tissue is relatively simple because the bladder is a relatively simple organ.
"I don't have to grow a bladder that is connected to nerve tissue and is able to be emptied volitionally," Kurzrock said. "Most of the children that I care for would be happy just to have a bigger bladder. This would reduce urine incontinence and protect their kidneys."
Funding for the study was provided by grants from Shriners Hospitals for Children and by the Children's Miracle Network. Other study authors include Deborah Lieu, Lea deGraffenried, Camie Chan and Roslyn Isseroff, all of UC Davis.
UC Davis Children's Hospital is the Sacramento region's only comprehensive hospital for children. From primary care offices to specialty and intensive care clinics, pediatric experts provide compassionate care to more than 100,000 children each year and conduct research on causes and improved treatments for conditions such as autism, asthma, obesity, cancer and birth defects. For more information, visit the UC Davis Children's Hospital Web site.