Hope Grows for Tissue Development

OSU researcher transforms stem cells into blood vessels

By Diane Clay

The Daily Oklahoman

October 01, 2002

STILLWATER - On the fourth floor of the Engineering North building at Oklahoma State University, a young researcher is developing what could become one of the most important life-saving processes ever created.

Sundar Madihally has already found a way to turn stem cells from umbilical cords into endothelial cells, which line the inside of blood vessels. Within five years, he hopes to create a process that will make blood vessels in large quantities. He plans to patent the idea.

His next project will be to turn the CD34 positive stem cells into tissue for livers and heart valves.

He said a similar process eventually could be used to create organ tissue, which would expand the pool of available tissue for patients who need transplants. Only about half of those patients find donors now, and many die.

"If I can create anything, I can save a lot of lives and improve the quality of life for a lot of people," Madihally said.

"It works out good for society and good for the state of Oklahoma."

Madihally, 31, joined the OSU faculty this year and brought his graduate work from Harvard Medical School .

Oklahoma was Madihally's first experience with the Midwest - an experience that convinced him to stay.

"People are really, really friendly. It's much better than being in Boston," he said.

Oklahoma and Stillwater are vastly different from Madihally's native home in Bangalore, India, one of that country's largest municipalities with more than 5 million residents.

He lived with his parents before heading to the United States in 1994 to get his master's degree at Wayne State University in Michigan.

He came to America, he said, because of better technology and research opportunities and, most importantly, because of the ideal that "if you work hard, you can come up in life."

He plans to return to India in November to marry his fiancee, then return to the United States to continue his research.

The basis of his work is CD34 positive stem cells, which are taken from umbilical cords after babies are delivered. They are not taken from aborted fetuses, a controversial practice that is tangled in political and religious battles.

Stem cells are vital to tissue creation, because scientists such as Madihally can program the cells to become whatever they want. The process allows doctors to use natural tissue instead of synthetic tissue or tissue taken from another person.

It is the advanced version of the research made famous with the photo of a mouse with a human ear growing on its back. That process, Madihally said, wasn't necessarily practical, but it showed the world that it was possible to grow tissue.

Researchers such as Madihally took the idea and built on it.

Madihally said the blood vessels he plans to create would provide vessels for thousands of surgeries performed each year on organs such as the heart.

He said about 300,000 blood vessel parts are used each year in the United States for heart bypasses and other vessel-related operations. Most of the vessels used now are taken from other parts of the body or made from synthetic materials.

Madihally discovered the stem cells' ability to grow into blood vessel cells somewhat by accident. While growing stem cells during research at Harvard, he noticed at the end of some studies that the cells had changed into endothelial cells, the same cells that make up the inner lining of blood vessels.

He took that graduate research, brought it to OSU and is now creating conditions for the new cells to grow in large numbers.

Madihally and several graduate and undergraduate students created a scaffold or framework for the cells to grow on. The scaffold will degrade and be replaced as the cells grow.

After the blood vessel process is complete and patented, Madihally plans to turn to creating cells for liver tissue and heart valves.

More than 100 people are added to organ donor lists each day in the United States as they wait for new livers, hearts, kidneys and lungs. Half of them never find a donor.

Thousands more need heart bypass surgeries requiring spare blood vessels, and others need new heart valves. For now, bypasses and other surgeries requiring blood vessels use synthetic tissue, a practice that can lead to infection and rejection.

"Any kind of a foreign material, if it stays in the body for a long time, it always has a potential to cause inflammation. It's a danger," he said.

"Bacteria can easily bind to them and cause infection. We avoid all of those problems (with the new tissue)."

For now, the stem cells are taken from umbilical cord blood stored or "banked" by foundations.

Ideally, Madihally said, stem cells would come from umbilical cord blood stored by families, so the blood has the same genetic makeup as the patient.

Some families already save blood at foundations. Harvesting the blood can cost several thousand dollars. Storing the blood costs about $75 to $100 a year. Madihally said the cost should come down.

As strange as the practice sounds, scientists said it would revolutionize tissue replacement and add years and quality to thousands of lives.

He is writing a textbook on therapeutic antibodies and hopes to create a process for blood vessel production by 2006.

"It's a widening technology that is really, really important. There are a lot of things we can do," Madihally said.

One of Madihally's undergraduate students is trying to grow teeth. Other researchers in Cleveland are creating bone and cartilage. A doctor in Philadelphia was able insert stem cells into a baby in the womb and cure the baby's immune deficiency disease, commonly known as the "bubble boy syndrome," before birth.

Joe Alexander, OSU's interim vice president of research, said such specialized research is part of a growing emphasis on biomedical engineering at the school and part of a broader task to deal with homeland security.

"The university always has in mind the interests of the public and sustains endeavors not only to benefit Oklahomans but people across the nation and around the world," Alexander said.

"Dr. Madihally's work is the kind that seeks to change for the better all of our lives and the lives of our children."

Madihally received a $45,000 a year grant for the next three years from the Oklahoma Center for the Advancement of Science and Technology to continue his research, and he expects more grants from the National Science Foundation.