Rebuilding a Human Organ in the Lab

Stone formation and Urinary infections are successfully treated with suitable surgery and intensive antibiotic therapy. Conditions like bladder tumours, bladder rupture in injuries and accidents and disorders due to multiple sclerosis, diabetes or spina bifida (where the spinal cord in the lower end is malformed) – that pose problems for treatment. Sometimes even bladder replacements are required. Scientists thought that biomedical research would help in these cases. This breakthrough in tissue engineering would definitely help such patients.

"This suggests that tissue engineering may one day be a solution to the shortage of donor organs for those needing transplants," said Dr. Anthony Atala, the lead researcher. He said he believes the work provides a model for growing other tissues and organs.

The bladder transplants, performed on seven patients aged 4 to 19, were being reported online recently in The Lancet medical journal. The research team at Children's Hospital in Boston did the first procedure in 1999 but wanted to make sure it would work on others. The results weren't announced while the doctors did the other surgeries and followed the progress of the last patient for almost two more years.

As an organ, the bladder is far simpler than the heart, kidney or the spleen. It is a hollow vessel with an outer layer of muscle cells and an inner layer of special cells called urothelial cells, which form an impermeable reservoir for urine.

While bladder muscle cells grow easily enough in the lab to make sheets, urothelial cells had challenged scientists for long. It was this difficulty that had made earlier researchers use a variety of substitutes as bags and artificial bladders.

Popular approach

These were bags made from skin, sheaths of connective tissue, the peritoneum ( which is the inner membrane lining of the abdominal cavity), the placental sheet, intestinal bits, and synthetic polymers such as silicone. Of all these, the most popular approach has been using patient’s own intestines, shape them into a substitute bladder and fit this on to the patient by surgery. Even though this has offered some relief, since this substitute material is from the intestine it starts absorbing, while it should only act as a storage vessel. It was at this stage that Dr. Atala, at Boston and Dr. David Mooney, at the University of Michigan began using the small piece of the bladder itself, and finding ways to expand it into a full-fledged bladder.

In 1998, they found the right combination of growth factors and nutrient mixtures that would make both the muscle cells and urothelial cells grow. They were successful in using these experiments on dogs. Based on these success, Drs.Atala, S.B.Bauer, S.Saken. J.J. Yoo and A.B. Retik now attempted to tissue engineering bladders for needy humans.

Now these experiments did not replace the entire bladder. But if you think of the bladder as a light bulb, his team replaced a large piece of the round part of the bulb. And they ultimately hope to do the whole bulb.

"It gives everyone in the field ... the evidence and encouragement they've needed to say this can be done," said Dr. Stephen Badylak, a University of Pittsburgh expert in tissue engineering.

Growing other organs will likely hold unforeseen challenges, however, since organs are so specialized in their functions, scientists stress.

Even for people with bladder disease _ and there are an estimated 85 million worldwide_ Atala's technique requires testing on more patients and for longer times, researchers say. Replacing an entire bladder would pose many more problems, including reconnecting urine tubes, blood supply, and nerve signaling, according to Dr. Steve Y. Chung, an Illinois urologist who wrote a commentary for The Lancet.

Still, he called the work "a tremendous, tremendous advance."

For the children and teenagers in the study, the transplants reduced leaking from their bladders _ a potentially big gain in quality of life. For 16-year-old Kaitlyne McNamara, the transplant has meant a new social life.

At the time of her surgery five years ago, her kidneys were close to failing as a result of her weak bladder. Now, they are working again, and she no longer wears a diaper.

Scientists, marveling at how animals like salamanders regenerate lost limbs, have long toyed with the futuristic possibilities of regrowing worn-out or injured human parts. Recent discoveries have transformed those hopes into an emerging reality.

Over the past decade, researchers began fashioning better scaffold-like platforms that hold growing cells and dissolve inside the body. The study of stem cells, which can mature into all the body's other tissues, has also supercharged progress in regenerative medicine.

The Boston researchers used a more mature cell type known as a progenitor. They first operated on the patients to remove bad tissue that made up more than half their bladders. They fished out muscle and bladder wall cells, seeded them on cup-like bladder-shaped scaffolds of collagen, and then let the cells reproduce in the lab for seven weeks. Starting with tens of thousands, they ended up with about 1.5 billion cells. The cell-bearing molds were then surgically sewn back to the remnants of the patients' original and partly working bladders, where the lab-nurtured cells kept maturing.

The rebuilt bladders, though, were up to three times more elastic and better at holding urine, the researchers report. In all seven patients, kidney function was preserved, the study said. The patients must still empty their bladders regularly with a tube but can avoid leaking in between.

"It's really science fiction at its best," marvels Tracy McNamara, the transplant teenager's mother and a nurse.

She used to worry about her daughter dying from kidney damage or urinary infections. That's all faded into the past.

We have to wait and observe how these techniques are transformed to other organs. But whatever it is, this is a very giant step in lab-growing the organ. Hitherto we are forced to use the Transplantation technique, which has its own limitations and is possible in cases of heart, liver, kidney, and cornea only.