ORLANDO—Researchers have succeeded in regenerating an entire urinary bladder in large mammals, according to new study findings presented here at the American Urological Association annual meeting.
To grow a replacement bladder, bladder progenitor cells are obtained, grown in culture, and seeded on a biodegradable bladder-shaped scaffold made from collagen and/or polyglycolic acid. The neo-organ is then implanted into the subject.
In a six-month study of 23 canines, researchers found that a “neo-bladder replacement construct” could regenerate the entire urinary bladder within six months after implantation. At around two months after implantation, the bladder wall structure consisted of urothelium, muscle, and serosa.
At six months, the regenerated bladder showed near-baseline capacity and cystographic findings, and the bladder wall showed near native pharmacologic and electrophysiologic functional responses. So far, re-searchers have found no abnormal tissue development, immune response, or evidence of systemic response to the neo-bladder regeneration.
“This treatment option essentially regenerates the patient’s own bladder, reducing the risk of rejection and the need for immunosuppressant drugs,” said Timothy Bertram, DVM, PhD, senior vice-president of Tengion Inc., of Winston-Salem, N.C. “If successful in human clinical trials, patients should expect to regenerate normal bladder structure and function.”
Tengion is conducting three phase II clinical trials of its neo-bladder technology at leading academic medical centers across the United States. One trial involves children with neurogenic bladder due to spina bifida. Another looks at adults with neurogenic bladder due to spinal cord injury. The third involves adult patients with overactive bladder and urge incontinence.
“What we are doing in the clinical trials right now is looking at augmentation. What that means is that instead of regenerating the entire bladder we are regenerating a majority of the bladder which is physiologically active in urine storage,” Dr. Bertram said.
Patients with advanced bladder disease often require cystectomy, and replacement bladders made from intestinal tissue have been used successfully. These types of replacement bladders, however, have been associated with many well documented complications, such as chronic urinary retention, hematuria, and infection.