Transplantation Without a Donor


Today, millions of patients with diseased or damaged organs are waiting for others to die so they may live. It's a race against time, and even when a patient receives a donated organ, there is up to a 40% chance that his or her body will reject it over time. It's a conundrum to which no one has the answer, but possible solutions are now in the pipeline.

Anthony Atala, M.D., director of tissue engineering for the urology program at Children's Hospital Boston, and his research team are creating new organs in the laboratory using patients' own cells. "Potentially, in the distant future, tissue engineering will allow patients in need of an organ transplant to receive one with little delay and better chances for acceptance," says Atala.

For more than a century, physicians have sought alternative solutions to help address the shortage of organs for those needing transplantation. In the United States alone, more than 10,000 children and adults undergo bladder replacement or repair surgery every year, making bladders a highly valuable commodity. Today, physicians are replacing diseased or damaged bladders by using tissue types similar but not identical to that of the tissue in need of replacement. For example, a bowel segment may be shaped into a substitute bladder. While this procedure offers much relief to patients, avoiding problems with rejection, complications often develop because nature has designed the bowel to absorb and the bladder to excrete. As a result, children who undergo this procedure end up absorbing substances they should be excreting. Thus, this solution essentially fixes one problem but creates another.

Tissue engineering can avoid such complications because patients' own cells are shaped, grown, and used to seed scaffolding in the shape of the organ. "The whole concept of tissue engineering is to use the patients' own tissue," says Atala.

"So far, the laboratory has been successful in creating bladder, urethral, and cartilage tissue. Other tissues we are tackling include that of the trachea, skeletal muscle, and kidneys," Atala adds.

The biggest challenge moving forward for Atala and his colleagues is determining how to increase the blood supply that will allow for the engineering of solid organs.

The bladder is essentially a hollow vessel composed of an outer layer of muscle cells and an inner lining of urothelial cells. To grow a new and healthy organ, such as the bladder, a three-dimensional biodegradable polymer mold in the shape of a bladder is used to bind and grow the tissue together. Researchers must take a small biopsy of the organ tissue, the size of a postage stamp, separate the cells and expand them in culture. Within six weeks, Atala and his researchers have enough cells to cover an entire football field.

"We take these cells that have been grown in the lab and begin seeding the mold to create a new organ. It is like baking a layered cake, one layer at a time," Atala explains.

After the mold has been seeded several times, the cells multiply and produce viable tissue until the right architecture takes shape. Once implanted in the body, over time, the blood cells begin to attach to the new tissue. Eventually the temporary scaffold deteriorates inside the body, leaving behind a healthy, functioning organ. Most important, because the original cells are harvested from the patient, the body will not reject the new organ.

Suppose, however, that a patient's organ is so badly diseased that it becomes nearly impossible to take the tissue to create a replacement.

"Employing the same technology used to clone Dolly, the sheep, one can clone cells," says Atala. This procedure requires one skin cell from a patient and a donor egg. Next, Atala and his collaborators take all the genetic material out of the egg so that only the eggshell is left, place the skin cell inside the eggshell, and burst it with electrical energy to expand the cells, which induces that one skin cell to become several cells.

"We now have a mass of cells that may have the potential to become various tissue types, and, ultimately, organs," says Atala. "At this stage one may take the cells and drive them to become different tissue types genetically identical to the patient's own tissue. By ethical standards this is not considered an embryo because it is not the union of a sperm and an egg, nor is it the union of a cell and egg. It is the union of a cell and an eggshell."

Atala's research efforts are inspired by his work as a pediatric urologic surgeon. Every day he sees disparity between the need for healthy tissues and organs and the supply. While some of the engineered tissues developed in his laboratory are being used in patients, much more testing must occur before other tissues are ready to enter human clinical trials.

There remains much to be discovered before tissue engineering can make the kind of difference Atala envisions, but he is certainly encouraged by its promising start.

This article originally appeared in DREAM, a publication of Children's Hospital Boston. Mary-Ellen Shay is a staff writer for Children's Hospital.

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